The epididymal fat pad was evaluated as a site of islet transplantation in a syngeneic murine model of diabetes by comparing the transplant outcomes to that of islets transplanted intraportal. Mouse islets engrafted on the intra-abdominal epididymal fat pad ameliorated streptozotocin-induced hyperglycemia with similar efficacy as grafts implanted intraportally. Mice that received as few as 50 islets, either intraportal or in the epididymal fat pad, displayed similar glucose tolerance curves. Bioluminescence imaging and glucose measurement showed stable luminescence signals and blood glucose levels for over 5 months in both transplant sites using transgenic luciferase-positive islets. Prompt recurrent hyperglycemia occurred in all mice after removal of the epididymal fat pad bearing the islet graft. Histological examination of the grafts showed well-granulated insulin containing cells surrounded by healthy adipocytes. This study indicates that the epididymal fat pad maybe a useful islet transplant site in the mouse model for effective glycemic control.