Background: Diabetic retinopathy (DR), a kind of diabetic microvascular complication, is the leading cause of visual impairment in adults aged 30 to 65 years. Despite rapid research progress, robust predictors to assess prospectively with high precision the risk for DR in individuals with diabetes are still lacking. We investigated the relationship between pyrimidine metabolites and disease, and find out the potential biomarkers for diagnosis. Methods: The study group consisted of 116 subjects who were divided to 3 groups: control (n = 41), type 2 diabetes without retinopathy (DM, n = 37), and with retinopathy (DR, 38). Biochemical and clinical parameters, concentrations of related metabolites, including of cytosine, cytidine, uridine, thymine, thymidine and 2'-deoxyuridine were measured in plasma of all participants. Results: There was a significant increase of concentrations of cytosine (p = 0.010), cytidine (p < 0.001) and thynidine (p<0.001) with DR compared to DM. The concentration of uridine, thymine and 2'-deoxyuridine did not change. Conclusions: The concentrations of cytosine, cytidine and thynidine may be useful for monitoring the progression of DR and evaluating the treatment. And cytidine has good sensitivity and specificity for diagnosis. (C) 2011 Elsevier B.V. All rights reserved.