In order to study the morphological aspects of endothelial regeneration and vascular wall reaction after microvascular anastomosis, rat femoral arteries were sectioned and successively sutured (end-to-end anastomosis) with microsurgical techniques. Control arteries and anastomosed vessels (recovered after 1, 4, 7, 14, 21, 30, 60, 120, 180 and 360 days) were studied by means of scanning (SEM) and transmission electron microscopy (TEM). The reendothelialization phenomena started after 7 days and were mainly evident at 21 days. Areas of subendothelial connective tissue with fibrin deposition remained exposed to the blood stream up to 21–30 days. Thrombus formations or post-anastomotic stenosis have been occasionally observed. Regenerating endothelium showed evident morphological differences from the control. These changes mainly consisted of shortened cell length, absence of pinocytotic vesicles, presence of cytoplasmic prolongations, and microvillous proliferations. The arterial wall showed subintimal thickening. The anastomotic site appeared completely covered by new endothelium after 30–60 days. Subintimal vascular wall changes (thickening of the media) as well as slight alterations of endothelial cells (shortened length, reduced number of pinocytotic vesicles) were evident in 60-day vessels. Lumen reduction, due to the protruding of endothelial-covered sutures, was occasionally observed in 60- to 120-day arteries. Endothelial cell morphology normalized after 60–120 days. However, thickening of the media and occasional lumen reduction were observed also after 180–360 days. Although the endothelial regeneration phenomena were clearly evident after 2 weeks, nevertheless the reestablishment of arterial wall took longer time. In fact, paralleled SEM and TEM observations made it possible to recognize three different kinds of arterial changes: (1) Temporary changes consisting of a highly thrombogenic exposed subintimal connective tissue (1–30 days) and of regenerating endothelium morphologically different from control endothelium (14–60 days); (2) permanent changes characterized by thickening of the media, and (3) occasional changes corresponding to reduction of the vessel caliber. Temporary changes may be shortened by adequate therapy. Endothelial changes may represent the sign of an impaired endothelial function. Permanent changes are due to a hyperplastic-inflammatory reaction, and are probably related to the natural history of arterial wall injury. Occasional changes may be related to poor microsurgical technique. Therefore, these alterations should be taken into consideration when setting therapeutic protocols and evaluating the reasons for arterial anastomosis failure.