The increased incidence of type 2 Diabetes Mellitus is associated with an impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin is a negative regulator of bone formation produced by osteocytes and there is recent evidence that its expression in serum is elevated in diabetic patients compared to control subjects. In this study, we test whether hyperglycemia affects serum and bone sclerostin levels in a rat model of type 2 Diabetes as well as sclerostin production by osteoblasts in culture. We used Zucker diabetic fatty (ZDF) male rats (n=6) that spontaneously develop obesity and frank diabetes around 8–9 weeks of age and