Introduction. Oxygen free radicals are involved in pathophysiology of ischemia/reperfusion (I/R) injury. This study was designed to assess the possible protective effect of pycnogenol (PYC) against I/R-induced oxidative renal damage. Materials and methods. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. PYC (10 mg kg(-1), i.p.) or saline was administered at 15 min prior to ischemia and immediately before the reperfusion period. At the end of the 3 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) activity were measured in the serum samples, while proinflammatory cytokines, TNF-alpha, IL-1 beta, and IL-6 levels were assayed in plasma samples. Kidney samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, Na+, K+-ATPase, and myeloperoxidase (MPO) activities, and the extent of tissue injury was analyzed microscopically. Results. Ischemia/reperfusion caused a significant decrease in tissue GSH level and Na+, K+-ATPase activity, which was accompanied with significant increases in the renal MDA level and MPO activity. Similarly, serum creatinine and BUN levels, as well as LDH and IL-1 beta, IL-6, and TNF-alpha levels, were elevated in the saline-treated I/R group as compared to saline-treated control group. On the other hand, PYC treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. Conclusions. Findings of the present study suggest that pycnogenol exerts renoprotective effects, via its free radical scavenging and antioxidant activities, that appear to involve the inhibition of tissue neutrophil infiltration.