We evaluated 433 transversely sectioned microvessels from 54 sural nerves of diabetic patients with (43) and without (11) polyneuropathy and compared the findings with those of 366 microvessels from 50 sural nerves from controls, spanning the same ages. Whereas the number of microvessels per square millimeter and lumen areas and their size distribution were not significantly different between diabetic patients and controls, striking changes of the vessel wall were found in the nerves of diabetic patients. Mural area containing reduplicated basement membranes and pericyte degeneration were significantly increased in diabetic when compared with control nerves. A very low frequency of microvessel degeneration and endothelial cell separation was also encountered but only in diabetics with polyneuropathy. The microvessel changes we have found in nerve largely confirm and strengthen our previous findings. This study provides additional strong support for the idea that the mural changes of endoneurial microvessels do not relate to aging but do relate to diabetes mellitus. The structural alterations of endoneurial microvessel mirror changes seen in diabetic retinopathy and are sufficiently severe that they may accompany and account for functional alterations of the blood-nerve barrier and endoneurial microenvironment. It remains to be shown whether and how these changes relate to the development of polyneuropathy.