SUMMARY: The alteration induced by diabetes on vascular permeability to serum albumin was investigated in the mesentery of streptozotocin-induced hyperglycemic rats. Double-tagged (¹²⁵ I and dinitrophenol-haptenated) heterologous albumin was intravenously administered in normal and hyperglycemic animals, and the extravasation of the tracer was evaluated by radioactivity measurements and by morphometry at the ultrastructural level using quantitative protein A-colloidal gold immunocytochemistry. The results demonstrate that diabetes induces a significant increase in the permeability of the mesentery vessels to albumin. This increase is due to a more efficient transport of macromolecules by endothelial plasmalemmal vesicles and not to leakier interendothelial junctions. Passage across the endothelial basement membranes did not appear to be restricted in either the control or diabetic condition. However, in diabetes, the mesothelial basement membrane appeared to become modified and to restrain the passage of albumin toward the peritoneal cavity. After 3 months of diabetes, the rats presented a net increase in the average diameter of the blood vessels localized in the mesentery arcada (macrovascular hyperplasy) and a notable angiogenesis, manifested at the level of the microvasculature in the mesenteric windows.