OBJECTIVE: To compare serum markers of oxidative stress with diabetic retinopathy severity RESEARCH DESIGN AND METHODS: This cross-sectional study compared patients with types 1 and 2 diabetes with control subjects in western New York and Pennsylvania. Retinopathy severity was graded from funduscopic fields based on the Early Treatment of Diabetic Retinopathy Study. Serum samples were analyzed for thiobarbituric acid-reacting substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, creatinine, HbA1, and triglycerides. Appropriate analysis of covariance models were performed. RESULTS: TBARS (P = 0.019), triglyceride (P = 0.004), and glucose and HbA1 (both P<0.001) levels were elevated in diabetic patients compared with those in control subjects. SOD (P = 0.003) and GSH-Px (P = 0.046) levels were lower in diabetic patients than in control subjects. No correlation existed between SOD levels and either glucose or HbA1 levels. No significant associations existed between levels of TBARS, SOD, or GSH-Px and severity of diabetic retinopathy There was a significant association between poorer visual acuity and worse retinopathy (P = 0.009), which was only partly explained by macular edema. CONCLUSIONS: Increased levels of TBARS and decreased levels of SOD and GSH-Px were found in diabetic patients compared with those in control subjects, but no significant associations were found between the levels of these substances and severity of retinopathy When duration and type of diabetes and serum HbA1 levels were taken into account, only visual acuity remained associated with more severe retinopathy.