Vitreous fluorophotometry has proved to be a useful method to evaluate the integrity of the blood-ocular barrier to fluorescein in clinical and experimental diabetes mellitus. Diabetic patients with or without background retinopathy had increased vitreous accumulation of fluorescein after intravenous injection when compared with age-matched controls. Streptozotocin-induced diabetes in rats increase vitreous fluorescein levels. In the rat, this abnormality was reversed with insulin therapy and with pancreatic islet transplantation. The breakdown of the blood-ocular barrier to fluorescein appears to be the earliest detectable ocular abnormality of diabetes.