Alternative sites to the liver for islet transplantation have been studied for a long time. Intramuscular islet transplantation appears to be an alternative site to the liver because of the ease of access. First islet autotransplantations were reported in patients after total pancreatectomies. The transplanted islets showed a proper revascularization and their function was observed for up to 2 years after the implant. However, only a few cases of autotransplantation and no allotransplantation have been performed. The aim of this study was to verify the feasibility of islet allotransplantation into muscles. In four patients affected by type 1 diabetes mellitus in which liver islet allotransplantation was contraindicated, human islets were transplanted into patients' arm muscle with local anesthesia. The surgery was minimally invasive, without complications. In one patient a moderate local inflammatory reaction was observed at the site of the implant, which resolved spontaneously within 4 days. Islet graft function was observed after transplantation in all patients, but it progressively disappeared in 3 out 4 patients within a short time. In this first ever-reported intramuscular pancreatic islet allotransplantation, the procedure appears feasible but new strategies must be envisaged to significantly improve islet engraftment and the long-term graft function.