The aim of the present study is to evaluate the extent of DNA damage in diabetes and metabolic syndrome and to assess the variations after supplementation with antioxidants. We used comet assay to measure DNA damage in freshly isolated lymphocytes from a total of 12 rabbits, distributed into four experimental groups (n = 3 rabbits per group): non-diabetic (control, G1), diabetic (G2), diabetic supplemented with vitamin C (G3), and diabetic supplemented with vitamin E (G4). Also their serum was isolated for estimation of parameters that contribute to metabolic syndrome. Malondialdehyde (MDA), the marker of oxidative stress was also assessed. Mean values of DNA damage (tail length, expressed as mum), lipid peroxidation and concentration of blood glucose, MDA, C-reactive protein, and triglycerides were higher in G2; whereas the mean values of concentration of high-density lipoprotein, serum paraoxonase-1 activity and small dense low-density lipoprotein oxidation time were reduced in G2 followed by G3, G4, and G1. A significant positive correlation was observed between the DNA damage and elevated parameters of metabolic syndrome (r = 0.66, 0.96, 0.89, 0.75, 0.88, 0.92, 0.99, P < 0.05) and a significant negative correlation (r = -0.91, -0.75, -0.98, P < 0.05) was found between the DNA damage and declined parameters of metabolic syndrome. These data indicate that the extent of DNA damage is more in diabetic rabbits as compared to the non-diabetic or antioxidant supplemented group. Abnormal metabolic parameters and their correlation with DNA damage, suggest the risk of development of metabolic syndrome in diabetic group but a possibility of repression by antioxidants because of their ability to counteract oxidative stress.