Acute renal failure (ARF) is a common problem that affects both young and adult populations. Renal ischemia/reperfusion (RIR) remains the major cause of ARF. Renal ischemia/reperfusion injury is observed in a variety of clinical situations such as liver and renal transplantation and heminephrectomy. It is believed that mortality due to RIR is attributed to both renal and extra-renal damage. This damage is mediated through many mechanisms as oxidative/nitrosative stress, inflammatory mediators, apoptosis and necrosis. Many herbal remedies have a widespread use in folklore medicine to treat common ailments due to their safety and effectiveness. Furthermore, many drugs in modern pharmacopoeia are derived from natural source. The current study was focused on: 1- Investigating the beneficial prophylactic antioxidant, antiinflammatory, anti-apoptotic and anti-necrotic effects of aqueous ginger extract (AGE) on the injury induced by RIR. 2- Assessment of the beneficial therapeutic antioxidant, antiinflammatory, anti-apoptotic and anti-necrotic effects of AGE on the injury induced by RIR. 3- Evaluating the relative effect of AGE to allopurinol due to its potent antioxidant activity, and an angiotensin II receptor blocker as losartan due to its role in prevention of kidney diseases and its powerful anti-inflammatory and antioxidant effects (protective and therapeutic effect) on the injury induced by RIR. 4- Identifying the distant deleterious effects of RIR injury on the brain tissue. Renal ischemia/reperfusion was induced experimentally in rats by bilateral renal pedicles (renal arteries and veins) occlusion for 1 hr, followed by 24 hrs of reperfusion. Experimental Groups Adult male albino rats were randomly distributed into the following groups: 1. Negative Control Group (n=8): Normal rats, received oral saline. 2. Sham Operated Control Group (n=16): Rats were randomly distributed into two equal groups: Group I: received saline orally. Group II: received carboxy methyl cellulose orally. 3. Ischemia /Reperfusion (I/R) groups (n=80): Rats were randomly distributed into 8 equal groups as follows: Group I: received saline orally and served as saline control group. Group II: received carboxy methyl cellulose and served as CMC control group. Group III: received i.p. losartan (80 mg/kg) in saline, the first and second doses were administered over 2 consecutive days, the third dose was administered 1 hr before the ischemic insult, then the last dose just before reperfusion. Group IV: received i.p. losartan (80 mg/kg) in saline, was administered twice, 15 min after induction of ischemia and immediately after starting reperfusion. Group V: received aqueous ginger extract (AGE) orally (500 mg /kg) in saline, the first and second doses were administered over 2 consecutive days, the third dose was administered 2 hrs before the ischemic insult, then the last dose just before reperfusion. Group VI: received aqueous ginger extract (AGE) orally (500 mg /kg ) in saline, was administered twice, 15 min after induction of ischemia and immediately after starting reperfusion. Group VII: received allopurinol orally (50 mg/kg) in CMC, the first and second doses were administered over 2 consecutive days, the third dose was administered 2 hrs before the ischemic insult, then the last dose just before reperfusion. Group VIII: received allopurinol orally (50 mg/kg) in CMC, was administered twice, 15 min after induction of ischemia and immediately after starting reperfusion. At the end of reperfusion period both blood samples (followed by serum preparation) and tissue samples (kidney and brain) were collected for measurement of the following parameters: Serum samples: 1. Renal function: serum urea and creatinine level. 2. Serum lactate dehydrogenase. 3. Serum C-reactive protein. Kidney tissue samples: 1. Renal NO level. 2. Renal eNOS activity. 3. Renal SOD activity. 4. Renal caspase-3 activity. 5. Renal MDA content. Brain tissue samples: 1. Brain TNF-α & IL-1β. 2. Brain reduced GSH. 3. Evans blue dye extravasations into brain tissue. The Following Results Were Obtained: I. The Effect of RIR on the Measured Parameters Can Be Summarized as Follows: Renal ischemia/reperfusion (RIR) caused significant increase in serum levels of creatinine, urea, C-reactive protein (CRP) and lactate dehydrogenase (LDH). Moreover, RIR caused significant elevation in renal malondialdehyde (MDA), indicating occurrence of lipid peroxidation. Total renal nitric oxide (NO) content and renal caspase-3 activity were also increased, indicating apoptotic response. A significant reduction in renal superoxide dismutase (SOD) activity and in renal endothelial nitric oxide synthase (eNOS) activity were observed indicating, oxidative stress. Furthermore, RIR caused a significant decrease in brain reduced glutathione (GSH) content and significant elevation in brain tumor necrosis factor alpha (TNF-α) and in brain interleukin-1 beta (IL-1β). II. The Effect of AGE (500 mg/kg) Prophylaxis Compared with RIR: Prophylaxis with AGE resulted in a significant decrease in serum creatinine, urea, CRP and LDH levels. Furthermore, AGE treatment resulted in a significant reduction in renal MDA content while, renal caspase-3 activity was non significantly reduced. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, it resulted in a significant elevation in brain reduced glutathione (GSH) content while, brain TNF-α and IL-1β were not affected. III. The Effect of AGE (500 mg/kg) Treatment Compared with RIR: Treatment with AGE resulted in significant decrease in serum creatinine, CRP and LDH levels, while serum urea level was nonsignificantly changed. Furthermore, AGE treatment resulted in significant reduction in renal MDA content and renal caspase-3 activity. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, there was a significant elevation in brain reduced glutathione (GSH) content and a significant reduction in brain tumor necrosis factoralpha (TNF-α) and in brain interleukin-1 beta (IL-1β). IV. The Effect of Losartan (80 mg/kg) Prophylaxis Compared with RIR: Prophylaxis with losartan resulted in significant decrease in serum creatinine, CRP and LDH levels, while serum urea level was nonsignificantly decreased. Furthermore, losartan treatment resulted in a significant reduction in renal MDA content but renal caspase-3 activity was non significantly reduced. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, it resulted in a significant elevation in brain reduced glutathione (GSH) content and significant reduction in brain tumor necrosis factor alpha (TNF-α) and in brain interleukin-1 beta (IL-1β). V. The Effect of Losartan (80 mg/kg) Treatment Compared with RIR: Treatment with losartan resulted in significant decrease in serum creatinine, CRP and LDH levels, while serum urea level was not affected. Furthermore, losartan treatment resulted in a significant reduction in renal MDA content and renal caspase-3 activity. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, it resulted in a significant elevation in brain reduced glutathione (GSH) content and significant reduction in brain tumor necrosis factor alpha (TNF-α) and in brain interleukin-1 beta (IL-1β). VI. The Effect of Allopurinol (50 mg/kg) Prophylaxis Compared with RIR Prophylaxis with allopurinol resulted in significant decrease in serum creatinine, CRP, urea and LDH levels. Furthermore, Allopurinol treatment resulted in significant reduction in renal MDA content, while renal caspase-3 activity was not affected. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, it resulted in a significant elevation in brain reduced glutathione (GSH) content and significant reduction in brain tumor necrosis factor alpha (TNF-α) but brain interleukin-1 beta (IL-1β) was non significantly reduced. VII. The Effect of Allopurinol (50 mg/kg) Treatment Compared with RIR: Treatment with allopurinol resulted in significant decrease in serum creatinine, CRP, urea and LDH levels. Furthermore, Allopurinol treatment resulted in significant reduction in renal MDA content and renal caspase-3 activity. Moreover, it resulted in significant increase in renal NO, eNOS and SOD activities. In addition, it resulted in a significant elevation in brain reduced glutathione (GSH) content and significant reduction in brain tumor necrosis factor alpha (TNF-α) and in brain interleukin-1 beta (IL-1β). Based on The Previous Results, The Following Can Be Concluded: This study showed that, after further clinical investigations, 1- Ginger as well as allopurinol and losartan have antioxidant, anti-inflammatory, anti-necrotic, anti-apoptotic and cytoprotective effects against lipid peroxidation and nitrosative stress by increasing eNOS activity so they can be used in prevention and treatment of renal ischemia reperfusion injury, 2- Also, they can be used in prevention and treatment the distant deleterious effects of renal ischemia reperfusion on the brain, due to their anti-inflammatory and antioxidant effects. Recommendations: This study recommended that aqueous ginger extract can be used in treatment and prevention of renal and distant injury induced by renal ischemia/reperfusion and this necessitates performing clinical investigations