The study was undertaken to analyze the effect of pioglitazone on superoxide dismutase (Cu, Zn- SOD), catalase ( CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione ( GSH), ascorbic acid ( AA), lipid peroxidation products (LPO) and protein carbonyl groups (PCG) in the heart of alloxan-induced diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. In diabetic animals, Cu, Zn- SOD and CAT were elevated by 60 and 55%, and 90 and 77% as compared to controls at 4 and 8 weeks, respectively. GSH-Px, GSSG-R and GSH were diminished by 11, 14 and 33% as compared to controls at 4 or 8 weeks. AA was diminished by 52 and 41%. At P < 0.05, pioglitazone normalized the activities of Cu, Zn- SOD, GSH-Px and GSSG-R. The activity of CAT was modified as compared to diabetic non- treated rabbits. After pioglitazone treatment, GSH and AA were increased as compared to diabetic non- treated animals. In diabetic rabbits, LPO was elevated by 52 and 111% and normalized by pioglitazone treatment. PCG was elevated by 72 and 133% and diminished as compared to diabetic non-treated animals at 8 weeks. The study shows that pioglitazone reduces oxidative stress in the heart of diabetic rabbits. In therapy, similar action can improve the cardiovascular system of diabetic patients.