Capillary occlusions are characteristic features of the early diabetic retinopathy and are presumed to initiate neovascularization. Activated leukocytes can cause microvascular occlusions and cell damage by release of cytotoxic products. To explore the role of leukocytes in capillary occlusion, nonperfusion, and neovascularization of diabetic retinopathy, a rat model was used, in which a diabetic state was induced by alloxan. Retina flat preparations were differentially stained for monocytes and granulocytes. Capillary occlusion, nonperfusion, and neovascularization were assessed microscopically in the center, midperiphery, and periphery of the retina. In contrast to control retinas, 2- to 9-month diabetic rats showed many capillary occlusions by leukocytes, especially monocytes, endothelial cell damage, extravascular macrophage accumulation, and tissue damage. The percentage of activated monocytes and granulocytes in the circulating blood of diabetic rats was greatly increased, and areas of capillary 'loss' and neovascularization in the retina coincided with sites of extravascular leukocytes. The authors' results suggest a potential role of monocytes and macrophages in the pathogenesis of diabetic retinopathy.