Background: Renal ischemia/reperfusion is an imperative cause of acute kidney damage which in turn releases detrimental mediators into the circulation leading to subsequent remote organ injury. Aim of the study: to assess the possible protective effects of diacerein (DIA), an interleukin-1 receptor antagonist, against renal ischemia/reperfusion (I/R) induced kidney and lung injuries in male albino rats. Material, Methods: Rats were randomly assigned into: sham, I/R, and DIA-pretreated I/R groups. DIA was orally administered in doses of 25, 50 and 100 mg/kg/day for 20 days, then, both right and left renal pedicles were clamped for 45 min followed by reperfusion for 24 h. One-way ANOVA followed by Post-Hoc test were used to compare the results. P-Value of <0.05 was considered as statistically significant. Results : DIA significantly reduced serum creatinine and blood urea nitrogen (BUN), improved both kidney and lung histoarchitecture, reduced pulmonary interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), osteopontin (OPN), elevated superoxide dismutase(SOD), glutathione (GSH), nuclear factor erythroid 2–related factor 2 (Nrf-2), Heme oxygenase 1 (HO-1), and reduced malondialdehyde (MDA) lung levels. Conclusion: Our results show that DIA has a promising protective impact against kidney and lung injuries prompted by renal I/R. This effect is proposed to be mediated, partially, by downregulation of osteopontin and upregulation of Nrf-2/HO-1.