To examine whether the level of erythrocyte aldose reductase is a risk factor for the severity of diabetic retinopathy, the enzyme level in 97 non-insulin-dependent diabetes mellitus (NIDDM) patients was measured by the two-site enzyme-linked immunosorbent assay. Based on the results of fundus photography and biomicroscopy, the severity of retinopathy was classified among NIDDM patients of more than 10 years. The level of erythrocyte aldose reductase was significantly higher in the patients with active proliferative retinopathy than in those with nonproliferative or quiescent proliferative retinopathy. Multivariate logistic regression analysis demonstrated that the level of erythrocyte aldose reductase was an independent risk factor for active proliferative retinopathy (odds ratio, 1.28; 95% confidence interval, 1.01–1.61). The results suggest that a high level of erythrocyte aldose reductase in NIDDM patients may affect the prognosis of diabetic retinopathy. Patients with high enzyme levels would need to be closely followed up in the management of the retinal complication.