Abstract: The aim of this study was to determine the effects of dietary antioxidant supplementation with a-tocopherol and a-lipoic acid on cyclosporine A (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats were randomly assigned to either control, antioxidant (a-tocopherol 1000 IU/kg diet and a-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or cyclosporine π antioxidant treatments. Cyclosporine was administered for 7 days after an 8 week feeding period. Plasma was analysed for a-tocopherol, total antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, a-tocopherol and malondialdehye. Cyclosporine administration caused a significant decrease in superoxide dismutase activity (PϽ0.05 control versus cyclosporine) and this was improved by antioxidant supplementation (PϽ0.05 cyclosporine versus cyclosporine π antioxidant; PϽ0.05 control versus cyclosporine π antioxidant). Animals receiving cyclosporine and antioxidants showed significantly increased (PϽ0.05) catalase activity compared to both groups not receiving cyclosporine. Cyclosporine administration induced significant increases in plasma malondialdehyde and creatinine concentration (PϽ0.05 control versus cyclosporine). Antioxidant supplementation prevented the cyclosporine induced increase in plasma creatinine (PϽ0.05 cyclosporine versus cyclosporine π antioxidant; PϾ0.05 control versus cyclosporine π antioxidant), however, supplementation did not alter the cyclosporine induced increase in plasma malondialdehyde concentration (PϾ0.05 cyclosporine versus cyclosporine π antioxidant). Antioxidant supplementation resulted in significant increases (PϽ0.05) in plasma and erythrocyte a-tocopherol in both of the supplemented groups compared to non-supplemented groups. In conclusion, dietary supplementation with a-tocopherol and a-lipoic acid enhanced the erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine treated animals