Since the introduction of glucocorticoid-free immunosuppressive regimens, islet transplantation offers a less invasive alternative to pancreas transplantation. However, complications associated with intraportal islet injection and the progressive functional decline of intrahepatic islets encourage the exploration of alternative sites. Herein we evaluated, in the minipig, the use of the gastric submucosa (GS; group 1, n = 5) for islet transplantation compared with the kidney capsule (KC; group 2, n = 5). Subsequently we attempted to improve the vascularization of the submucosal graft (group 3, n = 5) by the addition of an extracellular matrix rich in growth factors (Matrigel). One month after grafting, we evaluated transplanted islet function in vivo and in vitro. Our study showed better function of islets engrafted in the GS than in the KC (P < .05). Despite the growth factors, Matrigel did not offer a more suitable environment to further improve engraftment (group 3, P < .05). Thus, even if the liver remains the gold standard, the GS represents a potential islet engraftment site, confirming the data obtained in vitro and in the rodent. Offering easy access by endoscopy, this site could constitute an interesting alternative for experimental studies in large mammals and, eventually, for clinical application.