Increased permeability of retinal blood vessels in human diabetic retinopathy is well known clinically. Its morphologic equivalent is unknown. In dogs with 5 years of poorly controlled alloxan diabetes and nonproliferative diabetic retinopathy comparable to that of man, permeability and patency of retinal blood vessels were tested with the protein tracer horseradish peroxidase and evaluated by electron microscopy. A breakdown of the blood-retinal barrier was found associated with extensive tracer leakage around retinal blood vessels. Tracer had seemingly permeated endothial junctions, and was not transported through the endothelial cytoplasm. Blood vessels which had lost their endothelial cells and were partially occluded by glial cells retained some patency to tracer. These findings suggest the following. (1) Endothelial tight junctions are not a static cell specialization but one that can open due to chronic metabolic or osmotic factors prevailing in diabetes. Opened tight junctions may account for plasma leakage seen clinically in human diabetic retinopathy. (2) In the absence of endothelial cells perfusion does not necessarily end abruptly. The tracer method and electron microscopy may show details of vascular obstruction that are not readily demonstrated clinically.