Intraportal islet transplantation has a long history as a procedure for clinical islet transplantation. However, many recent studies revealed that the intraportal procedure has some disadvantages in transplant efficiency and safety. Many candidates as an optimal transplant site for islets have been assessed, but further studies and clinical trials are still necessary. Intramuscular and subcutaneous spaces are important candidates, because the transplant and biopsy procedures are simple approaches with minimal invasion and few complications. Although they are sites with hypovascularity and hypoxia, which contribute to the poor transplant efficiency, many experimental trials for improving the outcome in intramuscular and subcutaneous islet transplantations have been performed, focusing on early angiogenesis and scaffolds for engrafting transplanted islets. We review current progress in intramuscular and subcutaneous islet transplantations and discuss ways to develop them as optimal transplant sites for islets. Copyright © 2013 John Wiley & Sons, Ltd.