Recent studies have demonstrated the benefits of osteocalcin (OCN) on glucose homeostasis and metabolic dysregulation. However, its role in body composition and vascular function remains unknown. This study was designed to examine changes in metabolic parameters and body composition as well as arterial stiffness after OCN treatment in type 2 diabetic rats. Adult male Sprague Dawley (SD) rats were fed chow or high fat diet (HFD) for 8 weeks, and then diabetes was induced with an injection of low-dose streptozotocin (STZ) and treated daily with intraperitoneal injections of OCN for 12 weeks. Our data showed that OCN treatment improved glucose homeostasis and lipid metabolism. Further analysis revealed that OCN treatment resulted in increased insulin sensitivity. In addition, untreated diabetic rats experienced significant weight loss, whereas OCN-treated rats better maintained body weight (300.75 +/- 38.14 g vs. 335.50 +/- 23.70, p = 0.005). OCN also changed body composition, as evidenced by reduced body fat mass, specifically abdominal fat mass. OCN-treated diabetic rats also demonstrated decreased pulse-wave velocity, indicating of improved arterial stiffness. Taken together, our findings in the current study revealed that OCN therapy prevents arteriosclerosis in an induced diabetic rat model by exerting beneficial effects on glucose levels, insulin sensitivity, lipid metabolites, and body composition changes.