Diabetic patients, both insulin-dependent (IDDM) and non-insulin dependent (NIDDM), exhibit abnormal antioxidant status, auto-oxidation of glucose and excess glycosylated proteins. Oxidative stress in diabetes leads to tissue damage, with lipid peroxidation and inactivation of proteins. Reduced antioxidant defenses in diabetic patients are associated with an increased risk of free radical mediated diseases. Dietary antioxidant compounds, including ascorbic acid, tocopherol offer some protection against these complications through their roles as inhibitors of glycation and as free radical scavengers. It has been reported that reactive oxygen generation in long standing diabetes may also result in oxidative damage to DNA. Also there is evidence to suggest that reactive oxygen is involved in the pathogenicity and complications arising from IDDM, but there is little to suggest a role of oxidative stress in the pathogenesis of NIDDM. In order to investigate this hypothesis further, peripheral blood samples were taken from 30 control individuals and 63 IDDM and NIDDM patients and examined by comet assay for DNA strand breakage. Statistically significant differences (p<0.05) were detected between control and diabetic patient groups. DNA damage in the comet assay was at higher level in NIDDM patients and slightly lower level in IDDM patients which may indicate that these cells are handling more oxidative damage on a regular basis. Also, a synergistic effect of smoking on DNA damage (with high levels of tailed nuclei) was observed in smoking diabetic patients in comparison with smoking non-diabetic controls.