• Fluorophotometry was used to evaluate the blood-ocular barrier in rats following streptozocin-induced diabetes, experimental systemic hypertension, sodium iodate treatment, diet-induced galactosemia, and aldose reductase inhibitors. After administration of intravenous (IV) fluorescein sodium, diabetes, hypertension, or sodium iodate treatment resulted in an increased vitreous accumulation of IV fluorescein. Accumulation of dextran-labeled fluorescein (3,000 and 19,000 molecular weight [mol wt]) was not increased in diabetic or sodium iodate-treated animals. However, 3,000-mol wt dextran-labeled dye accumulated in the vitreous of hypertensive rats. The disappearance of fluorescein injected into the vitreous was significantly delayed in diabetic and sodium iodate-treated rats, whereas this rate was normal in hypertensive animals. Galactosemia did not alter vitreous fluorophotometric measurements. Pretreatment for systemic effects with aldose reductase inhibitors did not correct the vitreous fluorophotometric measurements of diabetic rats.