Cyclosporin A (CsA) is one of the most efficient immunosuppressive drugs that are widely used in organ transplantation. However, its clinical use is often limited by acute and chronic nephrotoxicity. One of the possible mechanisms of CsA-induced nephrotoxicity is thought to be reactive oxygen species (ROS) formation. The present work was designed to investigate the potential protective effect of wheat germ oil (WGO) as antioxidant on CsA-induced nephrotoxicity in rats. It was found that treatment of animals with CsA alone significantly increased the levels of blood urea nitrogen and serum creatinine. In addition, CsA has also reduced the renal content of reduced glutathione, as well as the enzymatic activities of superoxide dismutase and catalase. Furthermore, these effects were associated with an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-kB expression. Moreover, histopathological examination showed severe damage of the renal tissue in animals treated with CsA alone. The present work demonstrates that administration of WGO 5 days before and concurrently during CsA administration ameliorated all these negative effects and improved renal function via inhibition of ROS, iNOS and NF-kB expression. Most interestingly, the immunosuppressive effect of CsA has not been affected by WGO.