Following transplantation, the microvascular endothelium and endothelial cells play a critical role in allograft rejection, as well as response to surgical trauma. In this study, endothelial-cell damage was assessed through microvascular permeability, and the role of surgical trauma was evaluated during the acute phase of limb allograft rejection. Eighteen isograft and 18 allograft composite-tissue transplantations were performed between 72 rats. At 24-hr, 72-hr, and 7-days follow-up, microvascular permeability, leukocyte activation, functional capillary perfusion, red-blood-cell velocity, vessel diameter, and an endothelial edema index were measured. The permeability index (PI) was statistically significantly greater in the allografts at all follow-up points, compared with the isograft controls (p <0.001). The number of rolling leukocytes was significantly greater in the allografts at 24 and 72 hr; the number of sticking and transmigrating leukocytes was greater at all three follow-up points; and the number of rolling lymphocytes was greater at 7 days (p <0.05). These findings demonstrate the increased rejection phenomenon in allografts, and the increased susceptibility to ischemia and reperfusion injury, compared with isograft transplants. Increased leukocyte activation and acute destruction of endothelial-cell barrier function were demonstrated during the acute rejection period following composite limb allotransplantation.