Introduction: Diabetic osteoporosis (DOP) is a widespread public health problem. The flavonoids of Rhizoma Drynariae (RDF) have a clear preventive and therapeutic effect on osteoporosis (OP), but it is not yet clear whether RDF has an anti-DOP and whether its mechanism is related to the activation of the BMP2/Smad signaling pathway. The current study aimed to study this effect of RDF in DOP rats and the possible involvement of the BMP2/Smad signaling pathway activation. background: Diabetic osteoporosis (DOP) is a worldwide public health problem with high prevalence. Methods: Following intragastric administration of RDF for 12 weeks, the body weight, blood glucose, and the bone histopathological changes detected by hematoxylin-eosin (H&E) and calcein staining were monitored, while bone parameters were regularly assessed from observations made by micro-CT. At the end of the experiment, the expression of Bmp2, Bmpr1a, Runx2, and Smad4/5 genes was detected by real-time PCR (RT-PCR). Meanwhile, western blotting or immunohistochemical staining monitored the protein expressions of BMP2, RUNX2, and SMAD5 in the bone. objective: The Rhizoma Drynariae flavonoids (DRF) has a clear preventive and therapeutic effect on osteoporosis (OP), but it is not clear whether DRF has the effect of anti DOP and whether its mechanism is related to the activation of BMP2/Smads signaling pathway is not clear and needs further research. Results: The results firstly indicated that RDF significantly alleviated the signs and symptoms of DOP, which manifested as improved body weight and blood glucose. As obtained from the results of histopathology and micro-CT, RDF could promote the formation of bone trabeculae and alter several the bone microstructure parameters, including an increase in the bone volume/total volume (BV/TV), connective density (Conn-Dens), and trabecular bone number (Tb.N), as well as a decrease in the trabecular spacing (Tb.Sp). The western blotting analysis and RT-PCR results also confirmed that RDF could markedly increase the mRNA expression levels of Bmp2, Bmpr1α, Smad4, Runx2, and Smad5 in the bone, as well as the corresponding protein expression levels of BMP2, RUNX2, and SMAD5. These results reveal that RDF can activate the BMP2/Smad signaling pathway, thus promoting bone remodeling in DOP rats. method: After intragastric administration of DRF for 12 weeks, body weight, blood glucose, and histopathological changes in the bone of DOP rats were monitored by hematoxylin-eosin (H&E) and calcein staining, and bone parameters was regularly computed after observating by using micro-CT. At the end of the experiment, the expression of BMP2, BMPR-1a, Runx2 and Smad4/5 genes were detected by RT-PCR. Meanwhile the protein expressions of BMP2, Runx2, and Smad5 in the bone were monitored by Western blotting or immunohistochemical staining. Conclusion: RDF can increase bone trabeculae and bone mineral density by promoting bone formation and inhibiting bone absorption, thereby playing a role in improving DOP. This effect is related to the regulation of the BMP2/Smad signaling pathway. result: The results firstly indicated that DRF could significantly alleviate the signs and symptoms of DOP, which manifested as improvement of body weight and blood glucose. Results from histopathology, DRF could promote the formation of bone trabeculae and increase the bone microstructure parameters BV/TV, Conn-Dens, Tb.N and decrease Tb.Sp. In addition, the experiments of Western blotting analysis, RT-PCR also further confirmed that DRF could markedly increase the mRNA expression of BMP2, BMPR1a, Smad4, Runx2, and Smad5 in the bone and related protein expressions of BMP2, Runx2, and Smad5. Those results suggested that DRF could activate BMP2/Smads signaling pathway, thus promoting the bone remodeling of the DOP. other: no