Pancreatic islets are normally richly blood perfused to meet the demands of the highly metabolically active beta-cells. When islets are isolated for transplantation the blood vessel connections are interrupted and after transplantation a new vascular system in the tissue needs to be formed. Meanwhile, many of the islet cells die from hypoxia. Several factors determine the extent of the cellular death in the immediate posttransplantation period. Such factors include the degree of metabolic activity of the cells, the oxygen tension in the implantation organ of choice and whether the islets are implanted singly or in clusters affecting oxygen tension gradients from surroundings into the graft. Beta-cell death can be limited posttransplantation by taking these factors into account, by targeting hypoxia-induced cellular pathways that cause apoptotic death and by increasing local oxygen supply e.g. by co-transplantation of oxygen carriers. The revascularization of transplanted pancreatic islets differs pending on implantation site, and e.g. in intraportally transplanted islets an impaired oxygenation with increased apoptotic cellular death seems to prevail for the first months. Revascularization can be improved by change of implantation site, by stimulating angiogenic factors or by inhibiting angiostatic factors in islets for transplantation. Bioengineering of islets for implantation with growth factors or auxiliary cells can induce or contribute to increased revascularization.