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We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate‐induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)‐injection. Curcumin prevented maleate‐induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate‐induced oxidative stress by increasing the nicotinamide–adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I‐dependent superoxide anion (O₂•^—) production, formation of malondialdehyde (MDA)‐ and 3‐nitrotyrosine (3‐NT)‐protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all …