Parcetamol is widely spread analgesic and antipyretic drugs and its overdose, which can cause severe damage to kidneys, is one of the most common reasons of emergency admissions. In this study we demonstrate the effects of pomegranate peel extract, on parcetamol nephrotoxicity, and the possibility of co-administration therapy of pomegranate peel extract and N-acetyl cysteine (NAC) to ameliorate paracetamol toxicity. Material and Methods: 50 adult male albino rats were equally divided into 5 groups as follow: Group I (Control animals): They received only balanced diet and tap water, Group II received paracetamol (treated group) at a single dose 400mg/kg.b.w/day orally, Group III in which each rat received orally paracetamol at same previous dose and N-acetyl cysteine at a single dose 150mg/kg.b.w/day orally, Group IV received paracetamol at same previous dose and pomegranate peel extract at a single dose 430 mg/kg.b.w/day orally and Group V received paracetamol , N-acetyl cysteine and pomegranate peel extract at same previous doses. After 28 day of treatment, venous blood samples were collected for assaying serum creatinine and urea levels. After that, rats were anaesthetized with intraperitoneal injection of phenobarbitone then sacrificed. Kidneys were collected for histopathological examination and immunohistochemical determination of proapoptotic caspase-3. Results: Paracetamol induced a highly significant increase in blood urea nitrogen and creatinine (p<0.001). Also all these alterations were confirmed histopathologically in the renal cortex and medulla where paracetamole induced separated and congested glomerular capillaries with wide Bowman's space. Cortical and medullary ducts show extensive vacuolation of their cytoplasm and intra-luminal eosinophilic homogenous material. The interstitium infiltrated by the inflammatory cells and vascular congestion was very prominant in-between tubules. Moreover, paracetamol led to apoptotic death in renal tubular cells, manifested by an increase in the expression of caspase-3. Meanwhile, N-acetyl cysteine and Pomegranate peel extract showed a protective action against paracetamol toxic effects especially when used in combination. Conclusion: It can be concluded that N-acetyl cysteine and Pomegranate peel extract had an ameliorating effect against Paracetamol nephrotoxicity in adult male albino rats.