Introduction: Type 2 diabetes (T2D) has been linked to increased fracture risk, despite normal or high bone mineral density (BMD). High circulating levels of osteoprotegerin (OPG) might be related to increased fracture risk. The trabecular bone score (TBS) is a measure of bone microarchitecture and low TBS has been linked to poor bone quality. Aim: The aim was to evaluate quantitative and qualitative parameters linked to bone structure in post-menopausal women with T2D. Methods: N=170 post-menopausal women, n=123 with T2D (mean age 65.4±10.7 years, BMI 28.7±4.3 kg/m2) and n=47 control subjects (mean age 59.4±4.7 years, BMI 26.6±4.8 kg/m2) have been enrolled. Exclusion criteria were: anti-hyperglycemic medications other than metformin; drugs affecting bone metabolism; bone diseases; hyperparathyroidism; hyperthyroidism; liver failure; chronic kidney disease; alcohol and drug abuse. Circulating levels of OPG were measured (Bio-Rad Laboratories, Inc, CA, USA). The TBS was calculated with a software (TBS iNsight; Medimaps Group, Switzerland) applied to the Dual Energy X-ray Absorptiometry images of the lumbar spine (DXA, Hologic, Canada). Results: BMD values did not differ between patients with T2D and control subjects after adjustment for age and BMI. OPG was higher in T2D than in control group (526.56±209.91 pg/ml vs 368.20±198.16 pg/ml; p<0.001), even adjusting for BMI (518.74±18.13 pg/ml vs 400.61±30.21 pg/ml; p=0.001). In T2D group significant positive correlations were observed between OPG and glycemia (p=0.048), glycated hemoglobin (p=0.018) and disease duration (p<0.001). In T2D group TBS was inversely correlated with disease duration (p<0.001). In the total sample, OPG positively correlated with age (p<0.001), glycemia (p=0.048), interleukin-1β (p<0.001), tumor necrosis factor-α (p<0.001), sclerostin (p<0.001). A negative correlation was observed between OPG and TBS (p=0.001), even adjusting for age and BMI (β -306.2 [-611.47, -0.93, 95% CI], p=0.049). In multivariable regression model, T2D, higher age, higher waist circumference, and higher femoral and lumbar BMD were independent predictors of lower values of TBS. Conclusions: Serum OPG was higher in T2D group than in control group, and higher values of OPG might be linked to lower bone quality. Presence of T2D was associated with lower TBS. The TBS is an emerging marker of bone quality with potential clinical usefulness in fracture risk assessment in T2D.