Toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. The present study was designed to investigate the effects of Pongamia pinnata (PP) leaves, a plant rich in flavonoids in I/R induced renal failure in rats. Antioxidant activity of the hydro-alcoholic extract of Pongamia pinnata was determined by DPPH free radical, and Hydroxyl radical scavenging assay. The protective effect of Pongamia pinnata leaves against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Animals were subjected to occlusion of both the renal pedicles for 45min followed by 24h of reperfusion. Pongamia pinnata hydro-alcoholic leaf extract (100 mg/kg, 200 mg/kg and 400 mg/kg, p.o.) was administered 8 weeks prior to ischemia. At the end of the reperfusion period, rats were sacrificed. Malondialdehyde (MDA), reduced glutathione (GSH) levels, catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine, Serum Cystatin C, serum oxaloacetate transaminase (SGOT), serum pyruvate transaminase (SGPT), blood urea nitrogen (BUN) and Lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with Pongamia pinnata hydro-alcoholic leaf extract markedly attenuated renal dysfunction, morphological alterations, reduced elevated malondialdehyde levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R induced renal injury and Pongamia pinnata leaves exert renoprotective effects probably by the radical scavenging and antioxidant activities. Key words: Pongamia pinnata, hydro-alcoholic leaf extract, antioxidant, renal ischemia