Lithium is widely used for treatment of behavioral disorders and has been shown to possess insulin-mimetic properties. The present study examines the in vivo effects of lithium alone, as well as in combination with vanadate (a potent insulin-mimetic agent), on the altered antioxidant status in the liver and kidney of diabetic rats. The elevated blood glucose levels in diabetic rats were about 50% restored by oral administration of lithium (0.3 mg/ml) and were completely normalized following vanadate addition (0.05 mg/ml) to lithium. Lithium therapy effectively normalized the decreased activities of catalase (CAT) and glutathione peroxidase (GSH-PX) but could not restore the lowered superoxide dismutase (SOD) in the liver of diabetic rats; while in kidney, the treatment proved to be ineffective. Inclusion of vanadate produced synergistic effect and caused partial restoration of the altered CAT, GSH-PX and CuZn-SOD levels in diabetic kidney and the depressed SOD activity in diabetic liver. These results suggest that lithium therapy may prove effective in improving the impaired antioxidant status during diabetes and vanadate supplementation at a low dose potentiates the effectiveness of lithium action.