To analyze the effect of psoralen on osteoporosis(OS) rats based on Wnt/β-catenin signaling pathway.Methods:A total of 78 SD rats were randomized into the control group(n=13) and modeling group(n=65).Bilateral ovariectomy was performed to induce OS in rats in the modeling group and rats in the control group received sham operation.The model rats were randomly classified into model group，alendronate sodium group，and low-concentration，medium-concentration，and high-concentration psoralen groups，with 13 rats in each group.The model group and control group were given double distilled water and alendronate sodium group received 0.2 mg/mL alendronate sodium.The low-concentration，medium-concentration，and high-concentration psoralen groups were treated with 0.4 mg/mL，0.8 mg/mL，and 1.6 mg/mL psoralen，respectively.Each group received intragastric administration at 5 mL/kg，qd，for 12 weeks.The bone mineral density(BMD)，trabecular thickness(Tb.Th)，trabecular number(Tb.N)，trabecular seaparation(Tb.Sp)，levels of osteoprotegerin(OPG) and osteocalcin(BGP) in serum and bone tissue，and expression of low density lipoprotein receptor-related protein 6(Lrp6)，glycogen synthase kinase 3 beta(GSK-3β)，β-catenin，and runt-related transcription factor 2(Runx2) in bone tissue were detected and compared.Results:Compared with model group，the administration groups showed high BMD of the 4th lumbar spine and left and right femur，large Tb.Th and Tb.N，low Tb.Sp，high OPG level and low BGP level in serum and bone tissue，high mRNA level of Lrp6，β-catenin，and Runx2，and low GSK-3β mRNA level，and the changes of the above indexes were dose-dependent in psoralen groups，with significant difference(P<0.05).Conclusion:Psoralen can increase BMD and level of OPG in serum and bone tissue，decrease the level of BGP，raise Tb.Th and Tb.N，and reduce Tb.Sp in OS rats in a dose-dependent manner.The mechanism is the likelihood that it activates the Wnt/β-catenin signaling pathway.