Background: Cyclosporine A (CsA) is a nephrotoxic immunosuppressive drug. Antioxidants might attenuate its toxicity. In the present study, the effects of vitamin E and quercetin on the morphology of kidney in CsA-treated rats were investigated. Methods: Six groups of rats were used in this gavage feeding study either for 4 or 8 weeks. Groups 1 and 2 received either olive oil or 25% ethanol in olive oil per day. Group 3 received CsA (25 mg/kg/day) in olive oil. All other groups received CsA plus the following: group 4, vitamin E (100 mg/kg/day) in olive oil; group 5, quercetin (15 mg/kg/day) in 25% ethanol in olive oil; and group 6, vitamin E plus quercetin. In the final day of the study, the animals were sacrificed and kidney sections were prepared for morphologic studies using light microscopy. Results: Acute morphologic alterations induced by CsA in the kidney tubules included isometric vacuolization, brush border loss, microcalcification, and presence of inclusion bodies. Smooth muscle degeneration and necrosis were developed in arterioles. Treatment with vitamin E plus quercetin prevented severe, moderate, and mild abnormalities of the tubules. However fibrosis was the only microscopic change of the interstitium that was not present in animals treated with vitamin E plus quercetin after both periods.Some mild morphological changes of the blood vessels such as arteriolar medial smooth muscle degeneration and necrosis, arteriolar myocyte dropout and arteriolar wall hyalinization caused by CsA disappeared with administration of vitamin E, quercetin or vitamin E plus quercetin in both periods. Conclusion: Co-administration of vitamin E plus quercetin with CsA in renal transplant patients may be beneficial in reducing the nephrotoxic effects of CsA.