The study aimed to evaluate the efficacy of the porcine small intestine submucosa extracellular matrix (SIS-ECM) in a murine model, as a possible vascular patch for clinical use in reconstructive vascular and potentially cardiac surgery. Fifteen adult male Sprague Dawley rats and five green fluorescent protein (GFP) rats were enrolled in this study. The SIS-ECM graft (6 mm long, 4 mm wide) was implanted for patch plasty on the abdominal aorta of the animal, after excising part of its anterior wall. Histology and immunohistochemistry were used to evaluate the results at 15, 30, 90 and 180 days post-surgery. Graft re-population was demonstrated 15 days after implantation. The luminal surface of the regenerating tissue was partially covered by endothelial cells, and intimal hyperplasia occurred in the central part of the graft. Complete re-endothelialization of the patch with smooth muscle cells colonizing the graft and acting as the neoaortic wall was observed after 30 days. Near complete absorption of the biomaterial was observed after 180 days. No inflammatory cell reaction occurred. All animals survived and no graft aneurysm was observed. A SIS-ECM patch allowed the colonization of host endothelial and smooth muscle cells in the graft. This material may be an ideal substitute for reconstructive vascular surgery, and its use could be extended to surgical repair of cardiac defects.