This study investigated the nephroprotective effect of curcumin against acetaminophen (APAP)induced nephrotoxicity in rats. APAP-induced nephrotoxicity was evident by a significant increase (P<0.01) of urea and creatinine in serum. Furthermore, a significant increase (P<0.01) of lipid peroxidation as malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC) contents, interleukin-1β(IL-1β) and tumor necrosis alpha (TNF- α)accompanied by a significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and glutathione (GSH) content were observed in the kidney tissues. In addition, the cytochrome- P2E1 (CYP2E1) and inducible nitric oxide synthase (iNOS)gene expression ratios showed a significant elevation (P<0.01) in the kidney tissues. Oral administration of curcumin (100 mg/kg,b.wt.) ameliorated these adverse effects and showed nephroprotective activity against APAP toxicity. The nephroprotective activity of curcumin could be attributed to the regulation of the renal antioxidant balance, the down-regulation of CYP2E1 and iNOSgene expressions and the improvement of IL-1β and TNF-α levels. In conclusion, oral administration of curcumin showed protective effect against APAP-induces nephrotoxicity in rats.