Retinal vessel changes were experimentally investigated by a combination of color fundus photography, fluorescein angiography, and histologic studies in beagles that were fed a 30% galactose diet for up to 66 months. Previously, we have described the appearance of pericyte ghosts, microaneurysms, acellular capillaries, and intraretinal hemorrhages in dogs fed a galactose diet for up to 36 months. These disorders were similar to those observed in humans with background diabetic retinopathy. We report herein that dogs fed galactose for 48 to 60 months experience retinal changes associated with the chronic occlusion of capillary beds and subsequent ischemia of the retina. These changes included the appearance of broad areas of nonperfusion, soft exudates (cytoid bodies), intraretinal microvascular abnormalities, occluded arterioles, preretinal and intravitreal hemorrhages, and apparent new vessel growth around the optic disc. The present study clearly demonstrates that the galactose-fed dog is an animal model in which advanced retinal changes develop, and these changes are similar to those associated with preproliferative human diabetic retinopathy.