['Neuron-specific enolase as a potential biomarker of diabetic retinopathy, a neurovascular disease, had not been fully explored. We aimed to investigate the relationship between NSE and diabetic retinopathy.', 'Participants included Type 1 and Type 2 diabetes patients and healthy controls (n = 392). In this cross-sectional study, diabetic retinopathy status was assessed by fundus photographs. Serum neuron-specific enolase was measured using an electrochemiluminescence immunoassay. Co-variables for diabetic retinopathy and neuron-specific enolase were obtained from fasting blood samples and interviewer questionnaires.', 'Neuron-specific enolase was slightly elevated in diabetic patients, in contrast to healthy participants, and obviously increased in diabetic patients with retinopathy compared with those without [8.3 (2.0) vs. 7.6 (1.5), P = 0.037 and 8.3 (2.0) vs. 9.5 (2.7), P = 0.004, respectively]. In addition, neuron-specific enolase levels increased with and were closely correlated to the stages of retinopathy without macular oedema [r = 0.60 (0.50-0.71), P = 0.002] and stages of macular oedema with comparable retinopathy [r = 0.58 (0.46-0.69), P = 0.006]. The association of neuron-specific enolase with diabetic retinopathy was independent [odds ration (OR): 1.31 (1.12-1.65), P = 0.017], after the diabetic state and other potential confounders affecting NSE levels were considered (e.g., HbA1c , duration, age, gender, renal status and medicines). The optimal cut-off point for serum neuron-specific enolase levels for differentiating between participants with diabetic retinopathy including macular oedema and those without was 9.3 μg/l, with a sensitivity of 67.5% and a specificity of 69.8%.'] Is serum neuron-specific enolase elevated as a novel indicator of diabetic retinopathy including macular oedema?