Background: Accumulating evidence demonstrates an association of type 2 diabetes mellitus (T2DM) and its microvascular complications with increased fracture risk. In this study, we aimed to evaluate the relationships between serum concentrations of bone turnover markers and the presence and/or severity of diabetic retinopathy (DR) among patients with T2DM. Methods: A total of 285 patients with T2DM comprising 168 patients without DR and 117 patients with DR were enrolled in the cross-sectional study. In the latter group, patients were further divided into patients of mild and severe DR stages. The biochemical parameters and bone turnover markers were determined in all participants. Results: This study found that serum levels of procollagen type 1 N-terminal propeptide (P1NP), a bone formation marker, and the bone resorption marker serum β-cross-linked C-telopeptide of type I collagen (β-CTX) were more decreased in diabetic patients with DR than in those without DR, with differences remaining significant (P < .05) in multivariate linear regression models after adjustments for multiple confounding factors. Osteocalcin and β-CTX levels were further reduced along with the severity of DR among participants with DR. Moreover, multivariate logistic regression analysis revealed that lower serum levels of P1NP and β-CTX were associated with higher odds for the presence of DR, while β-CTX was associated with the severity of DR. Conclusion: Our results suggest that the development of DR might be involved in the progression of T2DM-induced deficits in bone formation and resorption or vice versa. Follow-up studies and further research are necessary to validate the associations and elucidate the underlying mechanisms. K E Y W O R D S bone turnover markers, diabetic retinopathy, type 2 diabetes mellitus Yaxin An and Simo Liu contributed equally to this study.