Objective To detect the oxidative DNA damage in diabetic patients and to investigate the relationship of oxidative DNA damage with diabetes and diabetic nephropathy. Methods Single cell gel electrophoresis (SCGE) was used to detect the DNA strand breaks in peripheral blood lymphocytes, and oxidative DNA damage product and serum 8-OHdG were determined by a competitive ELISA in 47 cases, including 25 patients without diabetic complications, 22 patients with diabetic nephropathy and 25 normal control subjects. Results Diabetic patients showed greater oxidative damage to DNA. The percentage of comet cells and the length of DNA migration (comet tail length) of peripheral blood lymphocytes were significantly increased in patients with diabetes, and significantly higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P＜0.05). There was a significant increase in serum 8-OHdG in diabetic patients compared with normal subjects (P＜0.05). Moreover, serum 8-OHdG was much higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P＜0.05). Conclusion There is severe oxidative DNA damage in diabetic patients. Enhanced oxidative stress may be associated with diabetes, especially in patients with diabetic nephropathy.