BACKGROUND Physiologic regulation of glucose metabolism is different between donor and recipient of xenogeneic pancreatic islet transplantation. We sought to assess whether the capacity of donor islets to adapt to recipient metabolic requirements should be considered in determining the success of pancreatic islet xenotransplantation. METHODS Rhesus macaque hosts rendered diabetic by streptozotocin were transplanted with porcine islets into the liver. Porcine c-peptide and insulin levels as well as intravenous glucose tolerance test (IVGTT) were measured at intervals. RESULTS At 2 months after islet transplantation, glucose responses on IVGTT showed a normoglycemic pattern. There was a 2.48 fold increase in C-peptide level during the initial 15 minutes of IVGTT in normal monkeys: from 3.122 ng/mL at baseline to 7.728 ng/mL at 15 minutes. Monkeys transplanted with porcine islets showed 2.38- and 2.45-folds the initial increases in C-peptide on IVGTT at 2 and 4 months after transplantation, respectively. Histopathologic evaluation identified the host endothelial cells having well lined the vessels of the porcine islets in the monkey liver. CONCLUSIONS The glucose response on IVGTT of porcine islets engrafted in the monkey liver resembled the normal monkey pattern rather than that of pigs. The presence of monkey endothelial cells suggested that porcine islets were well adapted to the local environment of the recipient.