We investigated the potential nephroprotective effects of misoprostol (MP) on doxorubicin (DOX) induced renal injury using histologic and biochemical assessment of rat kidneys. We used 21 male rats divided into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was given 0.5 ml 0.9% NaCl and 1 ml 0.9% NaCl orally for 6 days. DOX was administered as a single dose of 20 mg/kg on day 3. MP was administered orally for 6 days. We found that treatment with MP decreased serum creatinine and blood urea nitrogen levels significantly. DOX increased the malondialdehyde level and decreased catalase, superoxide dismutase activities and glutathione level. These alterations were prevented in renal tissues by MP. MP also decreased NADPH oxidase-4 and caspase-3 levels. In the DOX + MP group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DOX group. Renal injury caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP.