The role of the pancreatic microcirculation in the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus remains poorly understood. Herein, a method is described for the ultrastructural investigation of the integrity of the pancreatic microvasculature. The method consists of histochemical detection and isolation of the islets followed by albumin and protein A-gold immunocytochemistry, whereby the distribution of endogenous albumin is used as a marker of endothelial integrity. This technique, applied to the study of spontaneously diabetic rats, reveals a selective increase in permeability of islet capillaries and post-capillary venules at the onset of diabetes, while acinar capillaries and arterioles remain intact. At 50 days of age, before the onset of diabetes, the microvasculature of diabetes-prone rats shows no alterations in permeability to albumin. When used in conjunction with morphometric analyses, this methodological approach may be useful for further studies in pathologic or experimental conditions involving the pancreatic microvasculature.