OBJECTIVE Accumulating evidence indicates that oxidative stress may play an important role in the pathogenesis of type 2 diabetes and its complications. Lycopene, a very potent antioxidant of carotenoids, has received considerable scientific interest in recent years for its potential role in the prevention of oxidative stress-related chronic diseases. This study was undertaken to investigate whether the serum levels of lycopene are altered between type 2 diabetic patients with and without diabetic retinopathy. METHODS A total of 71 patients with type 2 diabetes were analyzed and compared with 23 nondiabetic healthy controls. Serum lycopene concentrations were assayed using high-performance liquid chromatography. RESULTS Lycopene level was found to be significantly lower in diabetic patients than in controls (p = 0.021). In the diabetic group, subjects with proliferative diabetic retinopathy had significantly lower lycopene levels than subjects without diabetic retinopathy or with nonproliferative diabetic retinopathy. In the analysis of correlations, hemoglobin A1c were negatively correlated with lycopene (r = -0.345, p = 0.007) after multivariate adjustment. A stepwise linear multiple regression model revealed that age and hemoglobin A1c were significant determinants of lycopene. CONCLUSIONS Our findings show that measuring serum lycopene is a novel convenient method for evaluating oxidative damage. Diabetic patients, especially those with advanced diabetic retinopathy, had significantly lower serum lycopene levels; this suggests that lycopene may be helpful for the diagnosis, severity, and therapeutic evaluation of diabetic retinopathy.