The subcutaneous site is ideal for clinical islet transplantation because it has the advantage of being accessible and can be biopsied when needed. Sadly, the results at subcutaneous sites were disappointing. The reason for this failure is not known, but poor vascularization may play a role. We tested the hypothesis that islet grafts would do better if more vasculature or oxygen could be supplied. Six hundred isolated C57BL/6 mouse islets were syngeneically transplanted into inbred streptozotocin-diabetic recipients at a subcutaneous site on the back with (Group A, n = 6) or without (Group B, n = 8) postoperative hyperbaric oxygen (2.4 ATA, 100% O(2)) therapy, or at a calf muscle (Group C, n = 9). During 13-week posttransplantation follow-up, recipients' blood glucose decreased and body weight increased significantly in all 3 groups (P < .05). However, there was no significant difference among the 3 groups. At 13 weeks, the insulin contents of the graft was also comparable among the 3 groups. Our data indicate the following: (1) postoperative hyperbaric oxygen therapy did not improve the outcome of islet transplantation at a subcutaneous site; and (2) a muscular site was not superior to a subcutaneous site for islet transplantation.