Wistar strain rats were made diabetic by injection of streptozotocin and divided into three groups fed on different diets: conventional solid foods, a fructose-rich diet and a fructose-rich diet mixed with ONO 2235, an aldose reductase inhibitor. The retinas of these rats were examined in flat mount preparations after trypsinization. Microvascular changes such as capillary tortuosity, microaneurysms, pericyte loss, that are typical of diabetic retinal microangiopathy, were seen most frequently in the rats fed on the fructose-rich diet. The rats fed on the fructose-rich diet with ONO 2235 showed much less vascular change than the diabetic rats fed on the conventional food. Electron microscopy of the retina revealed localized thickening of the basement membrane of the retinal capillaries, and this was most frequent in the fructose-fed rats. However, in rats fed on fructose with ONO 2235 the changes of the basement membrane were slight. It was concluded that the aldose reductase inhibitor, ONO 2235, prevented development of diabetic microangiopathy, probably by suppressing the enzymatic activation of aldose reductase in the retina.