One week after a partial pancreatectomy, which did not affect glucose homeostasis, adult rats were autotransplanted with 500 isolated pancreatic islets beneath the renal capsule. Some rats were rendered diabetic with streptozocin (STZ) before being implanted with the islets, and other rats received no STZ and thus remained normoglycemic. The number of implanted islets was insufficient to revert hyperglycemia, but the STZ-induced diabetic animals were treated with insulin according to one of the following protocols: 1) one daily subcutaneous insulin injection for 28 days after transplantation; 2) insulin injection on days 1-14; 3) insulin injection on days 15-28; or 4) no insulin. Four weeks after transplantation, the blood perfusion of the islet grafts was determined by a microsphere technique. Continuous hyperglycemia after implantation of the islets significantly decreased the volume of the graft and the blood flow per volume compared with normoglycemic animals also receiving islet transplants. Insulin treatment counteracted the decrease in both of these values. This result was achieved regardless of whether the insulin treatment was maintained throughout the 4-wk period or only during the first or second half. The mechanism behind the impaired blood perfusion of the grafts during continuous hyperglycemia is unknown, but it may reflect an effect on the revascularization of the graft or on the intrinsic regulation of the blood perfusion of the graft.