Objective: The relationship between age at natural menopause and type 2 diabetes mellitus (T2DM) has yielded conflicting results, particularly when confounded by the presence of obesity. We therefore aimed to examine the association between age at natural menopause and development of T2DM and the influence of postmenopausal obesity status on this association. Design: The data for this study was derived from one center (Beijing) of the REACTION study. After screening through our inclusion and exclusion criteria, 2689 postmenopausal women who completed a 3-year follow-up were included. Logistic regression analysis was conducted to clarify the association of the age at natural menopause with the development of T2DM. Results: After adjustment for potential confounders, there was no significant association between the age at natural menopause and development of T2DM for all subjects. However, when subjects were stratified along the postmenopausal obesity status at baseline, in the presence or absence of obesity, we found a surprising contradictory association in two subgroups: late menopause (age >50 years) was associated with an increased risk (OR, 1.45; 95% CI, 1.02 to 2.05) of developing T2DM in the postmenopausal group without obesity, whereas we found a reduced risk (OR, 0.43; 95% CI, 0.27 to 0.71) in the postmenopausal group with obesity. Moreover, we found that early menopausal women (age >= 45 years) with postmenopausal obesity had the highest risk (OR, 2.10; 95% CI, 1.11 to 4.00) of developing T2DM compared with all other postmenopausal women. Conclusions: Postmenopausal obesity status may influence the association of age at natural menopause and the development of T2DM.