Objective: The intensive vascular supply in pancreatic islets enables ß-cell to regulate insulin secretion promptly in response to the change of blood glucose level. Angiopoietin-1 (Ang1) is one of the most potent factors which control angiogenesis during developmental and inflammatory condition. Recently a study reported that the overexpression of Ang1 in islets improved the engraftment rate of islet transplantation by enhancing revascularization. The aim of our study was to investigate the role of Ang1 on glucose homeostasis. Methods: We used inducible systemic Ang1 knock out mice and pancreas ß-cell specific Ang1 knock out mice. After 24 weeks of high fat diet, we tested insulin sensitivity and secretory function. Furthermore, we observed the islet morphology and ß-cell proliferation. Results: High fat diet for 24 weeks after systemic deletion of Ang1 at 10 weeks of age induced glucose intolerance in Ang1 null mice compared to wild type mice with no change in insulin sensitivity. The serum insulin concentration after 15 min of glucose challenge in vivo was lower in Ang1 null mice and glucose stimulated insulin secretion in the isolated islets from Ang1 null mice was also lower compared to wild type mice, suggesting that there might be a defect in insulin secretary function in Ang1 null mice. To further dissect this phenomenon, we investigated the state of glucose homeostasis in β-cell specific Ang1 null mice. β-cell specific Ang1 null mice still demonstrated glucose intolerance after 24 weeks of high fat diet compared to the wild type mice. In immunohistochemical staining, β-cell specific Ang1 null mice showed slight decrement in the β-cell area and Ki67-positive proliferating β-cell number. Conclusion: Ang1 might be a key molecule to regulate insulin secretion in obesity mice model. Further investigation on the exact mechanism how Ang1 contributes to insulin secretion in the β-cell is warranted in the future.