Type 2 diabetes mellitus (T2DM) is increasing in prevalence and its complications are potentially fatal. Recent studies suggest that long-term complications of T2DM include alterations of the bone, evident by a high coexistence rate of diabetes mellitus with both osteoporosis and different fracture types. Current measurements of fracture risk are based on bone mineral density (BMD) measured via dual-energy X-ray absorptiometry (DXA); however, this method does not measure bone quality and often underestimates fracture risk in T2DM. Optical coherence tomography (OCT) holds the promise of early detection of diabetic bone microarchitectural alteration and serves as a possible non-ionizing alternative to DXA. The aim of this study is to evaluate the viability of using OCT-derived attenuation coefficients as a method for differentiating between healthy and diabetic bones in a diagnostic process. A TALLYHO/JngJ mouse model of diabetes was used and compared to a healthy control SWR/J; the differences in bone structure and quality of the TALLYHO/JngJ model compared with SWR/J is well documented in the literature. OCT cross-sectional images of four ex-vivo mouse femurs, two healthy and two T2DM, were used to calculate attenuation coefficients. Coefficients were calculated for the anterior side and the posterior side of the femurs. The posterior side was used as a control for the anterior side of the same femur sample. The attenuation-based comparison between healthy and diabetic bones shows that it is possible to differentiate between healthy and diabetic bones (p = 0.002). No significant difference in attenuation between the anterior and posterior side (p = 0.543, T2DM and p =0.055, healthy) was found. These preliminary results indicate that OCT-derived attenuation coefficients have the potential to differentiate between healthy and diabetic bones in a mouse model of T2DM.