Perturbations in capillary endothelial cell function are early events in the pathogenesis of diabetic retinopathy. We used tritiated thymidine autoradiography to study the turn-over rate of retinal capillary endothelial cells in retinovascular preparations from normal, untreated diabetic and diabetic mice treated with pancreatic islet-cell transplants. Capillary endothelial cell turnover was significantly increased in poorly controlled diabetes and this increase was reduced by islet-cell transplantation. The prevention of excessive endothelial cell replication by tight control of hyperglycemia may help prevent the characteristic structural changes of diabetic microangiopathy, such as basement membrane accumulation.