OBJECTIVE：To study the effect of total flavonoids of Epimedium brevicornu on postmenopausal osteoporosis （PMOP）model rats based on BMP/Runx 2/Osx signaling pathway so as to confirm the mechanism of preventing and treating osteoporosis（OP）. METHODS ：By body mass stratification ，50 rats were randomly divided into sham operation group ，model group，E. brevicornu total flavonoids low-dose and high-dose groups [265，530 mg/（kg·d）]，estradiol group [0.09 mg/（kg·d）]， with 10 rats in each group. Except that sham operation group underwent sham operation ，PMOP model was established by ovariectomy and castration in other groups. After modeling ，they were given normal diet for 2 months and then given relevant medicine intragastrically for consecutive 84 d，once a day ；rats in sham operation group and model group were given equal volume of normal saline. After last medication ，bone mineral density （BMD）of femur and vertebrae of the right lower limb ，the number of trabecular bone （Tb.N），trabecular bone thickness （Tb.Th）and trabecular separation （Tb.Sp）of femur were determined in each group. The serum levels of Ca 2+，OC and P 1NP in serum were detected by ELISA. HE staining was used to observe pathological changes of femur. mRNA and protein expressions of BMP ，Runx2 and OSX in bone tissue were detected by RT-PCR and Western blotting. RESULTS ：Compared with sham operation group ，BMD of femur and vertebrae ，serum levels of Ca 2 +，OC and P 1NP， Tb.N and Tb.Th of femur ，mRNA and protein expression of BMP ，Runx2 and Osx in femur were decreased significantly in model group，while Tb.Sp of femur was increased significantly （P＜0.01）；the structure of trabecular bone was disordered and the fracture was obvious. Compared with model group ，above indexes of rats in administration groups were improved significantly （P＜ 0.05 or P＜0.01），and the effect of E. brevicornu total flavonoids was dose-dependent （P＜0.05）；the number of trabecular bone increased， arranged orderly and the structure was more brevicornu total flavonoids can improve OP ，the mechanism of which may be associated with com promoting the activity of BMP/Runx 2/Osx signaling pathway.