Background: Cyclosporine A (CsA) is a nephrotoxic immunosuppressivedrug. Antioxidants might attenuate its toxicity. Inthe present study, the effects of vitamin E and quercetin on themorphology of kidney in CsA-treated rats were investigated.Methods: Six groups of rats were used in this gavage feedingstudy either for 4 or 8 weeks. Groups 1 and 2 received eitherolive oil or 25% ethanol in olive oil per day. Group 3 receivedCsA (25 mg/kg/day) in olive oil. All other groups received CsAplus the following: group 4, vitamin E (100 mg/kg/day) in oliveoil; group 5, quercetin (15 mg/kg/day) in 25% ethanol in oliveoil; and group 6, vitamin E plus quercetin. In the final day of thestudy, the animals were sacrificed and kidney sections were preparedfor morphologic studies using light microscopy.Results: Acute morphologic alterations induced by CsA in thekidney tubules included isometric vacuolization, brush borderloss, microcalcification, and presence of inclusion bodies. Smoothmuscle degeneration and necrosis were developed in arterioles.Treatment with vitamin E plus quercetin prevented severe,moderate, and mild abnormalities of the tubules. However fibrosiswas the only microscopic change of the interstitium thatwas not present in animals treated with vitamin E plusquercetin after both periods.Some mild morphological changes of the blood vesselssuch as arteriolar medial smooth muscle degeneration and necrosis,arteriolar myocyte dropout and arteriolar wall hyalinizationcaused by CsA disappeared with administration of vitaminE, quercetin or vitamin E plus quercetin in both periods.Conclusion: Co-administration of vitamin E plus quercetinwith CsA in renal transplant patients may be beneficial inreducing the nephrotoxic effects of CsA