The islets of Langerhans have a dense vascular network, with highly specialized endothelial cells. Animal data suggest that failure to maintain an intact islet vasculature may be a key feature in the course of type 2 diabetes. To study the relationships between beta and endothelial cells, we created pancreatic chimeras. We grafted embryonic chick pancreases under the kidney capsule of severe combined immuno-deficient (SCID) mice. These inter species grafts enabled us to separately study endocrine (of avian origin) and endothelial (of murine origin) cells. Using this model, we have studied the impact of hyperglycemia on the interaction between endocrine and endothelial cells. Seven week-old female mice were made diabetic by a single intraperitoneal injection of streptozotocin (160mg/kg, in citrate buffer) and only the mice with random blood glucose level above 200mg/dl were further studied. Embryonic chick pancreases, obtained at day 14 post-incubation, were microdissected and grafted under the kidney capsule of SCID mice, one embryonic pancreas per mouse. Two weeks later, the transplanted pancreas was analyzed. The macroscopic vascularization was observed after a systemic injection of fluorescein. The microscopic graft vascularization, endocrine and exocrine differentiation were analyzed by immunohistochemistry. To better characterize the interaction between mouse and chick cells, we used an avian-specific retrovirus, the RCAS (Replication-Competent Avian sarcoma-leukosis virus long terminal repeat with a Splice acceptor) system, which can be used for stable transfection of dividing avian cells. This study was carried out along the principles of laboratory animal care. In control mice, two weeks after transplantation, the pancreatic mass had increased, and the graft was well vascularized. The pancreas was well differentiated with insulin, glucagon and amylase positive cells. The microvascularization was dense and of murine origin as detected by nestin immunohistochemistry, an endothelial marker that is specific for mouse, as shown in control experiments. 2) In hyperglycemic mice, the pancreatic development was decreased, whereas beta cell density was increased. In all experiments (n=5), we observed large blood-filled spaces suggesting abnormal blood vessels that were however not lined by murine endothelial, nestin-positive, cells. 3) In the first control RCAS experiments, we used an RCAS carrying the gene encoding the green fluorescent protein (RCAS-GFP). Chick pancreases were infected in vitro with the RCAS-GFP for 1 hour before transplantation. Two weeks later, we detected green fluorescence in the entire graft, whereas no fluorescence was detected in mouse tissues.