Objective To investigate the effects of epimedium sagittatum(EPI)on bone metabolism and tibial bone microstructure in osteoporosis(OP)rats.Methods Rats were randomly separated into Sham group,Model group,EPI low-dose(EPI-L)group,EPI high-dose(EPI-H)group,and EPI-H+YC-1(HIF-1α inhibitor)group.Bilateral oophorectomy was performed to construct an OP rat model.ELISA was applied to detect serum IL-10,IL-6,TNF-α,serum calcium(Ca),serum phosphorus(P),osteoprotegerin(OPG),osteocalcin(OCN),and alkaline phosphatase(ALP)in rats.Dual energy X-ray bone density instrument was applied to detect tibial bone density(BMD)in rats.Micro CT was applied to detect the microstruc-ture of tibia bone.HE staining was applied to observe the morphology of tibial tissue.Bone morphogenetic protein(BMP-2),RUNt-associated transcription factor 2(Runx2),and cysteine proteinase-3(cleaved)were detected by Western blot Protein levels of caspase-3,hypoxia inducible factor HIF-1α(HIF-1α),vascular endothelial growth factor(VEGF),and vascular endo-thelial growth factor receptor 2(VEGFR-2).Results Compared with the Sham group,the microstructure and tissue morphol-ogy of the tibia of rats in the Model group were obviously damaged,the ratio of tibial bone surface area to volume,trabecu-lar separation,serum IL-6,TNF-α,ALP levels,and tibial bone tissue cleaved caspase-3 protein expression level were obvi-ously increased(all P<0.05),the bone trabecular thickness,serum IL-10,OPG,OCN,S-Ca and S-P levels,tibial BMD,tibial bone tissue BMP-2,Runx2,HIF-1α,VEGF,and VEGFR-2 protein expression levels were obviously reduced(all P<0.05).Compared with the Model group,the damage to the microstructure and tissue morphology of the tibia of rats in the EPI-L and EPI-H groups was obviously reduced,the ratio of tibial bone surface area to volume,trabecular separation,serum IL-6,TNF-α,ALP levels,and tibial bone tissue cleaved caspase-3 protein expression level were obviously reduced(all P<0.05),the bone trabecular thickness,serum IL-10,OPG,OCN,S-Ca and S-P levels,tibial BMD,tibial bone tissue BMP-2,Runx2,HIF-1α,VEGF,and VEGFR-2 protein expression levels were obviously increased(all P<0.05).Compared with EPI-H group,the above indexes were partially reversed in EPI-H+YC-1 group(all P<0.05).Conclusion EPI can reduce inflammatory re-action,regulate bone metabolism balance,and improve tibial bone microstructure in OP rats,possibly by activating the HIF-1α/VEGF/VEGFR-2 signaling pathway.