Abstract: Background and Objectives: The nephrotoxicity due to gentamicin is well established in man and experimental animals. Silibinin a bioactive flavanone in milk thistle possess anti-inflammatory and antioxidant activity. Therefore, the present study investigated the renoprotective effect of silibinin against gentamicin induced nephrotoxicity in rats. Method: Thirty rats were randomly divided into five equal groups (n = 6). Group I served as a control and treated orally with vehicle and Group II as a gentamicin control and administered vehicle two days before and then treated with gentamicin intraperitonially (100 mg/kg/day) for eight days. Group III-V were received silibinin orally at three dose levels (20, 40 and 80 mg/kg/day) two days before and eight days concomitantly with gentamicin intraperitonially (100 mg/kg/day). The silibinin was suspended in CMC (1% w/v). At the end of the treatment urine and blood was collected to assess the kidney functions as well as renal tissue processed for antioxidant and histopathological study. Results: Eight days of gentamicin treatment significantly increased levels of BUN, serum creatinine and decreased urinary creatinine and creatinine clearance. Further it increased MDA levels and decreased SOD and CAT activity as well as GSH levels. Silibinin treatment (40 and 80 mg kg-1) reversed the gentamicin induced alterations dose dependently. Further necrosis and degenerative changes in glomeruli and tubules observed in gentamicin treated rats were significantly restored with silibinin treatment at a dose of 40 and 80 mg kg-1. Conclusion: Silibinin dose dependently protected the kidney functions and normalize biochemical parameters and histopathological changes.