The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (), impaired glucose regulation (IGR) (), and normal glucose regulation group (NGR) (), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) () and T2DM group (183.20 ± 56.53 pg/mL) (), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009, ) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.