Intraperitoneally injected alloxan determined long term hyperglycemia in a group of Syrian hamsters (35 hyperglycemic hamsters); transitory hyperglycemia, with recovery of normal blood glucose concentration but impairment of glucose tolerance test, was observed in a second group of alloxan-treated animals (70 normoglycemic hamsters). Microvascular permeability by fluorescent microscopy technique, capillary basement membrane thickening and pancreatic islet B, A, and D cell degranulation by computer-assisted microdensitometry were studied in Syrian hamsters at different intervals (30, 40, 60, 90, and 120 days) after intraperitoneal alloxan administration. Hyperglycemic groups showed increased permeability of venous microvasculature to high molecular weight dextran in 50%, 71.4%, and 100% of animals studied at 30, 40, and 60, 90, 120 days from treatment, respectively; indeed, they revealed pancreatic islet B cell degranulation and no capillary basement membrane thickening. Normoglycemic groups presented increased venular leakage in 28.5%, 42.8%, 71.4%, and 100% of animals investigated at 40, 60, 90, and 120 days after treatment, respectively; moreover, they showed moderate pancreatic islet B cell degranulation and no capillary basement membrane thickening. In conclusion, more severe microvascular alterations seemed to be related to more severe impairment of glucose metabolism and to longer duration of diabetes; even in normoglycemic hamsters with pathological glucose tolerance test, enhanced permeability developed.