To investigate the effects of isopsoralen on bone metabolism in rats through PPAR-gamma-Axin2-Wnt signal regulation.Methods:A total of 40 female rats were randomly divided into a model group and an isopsoralen group with 20 rats in each group.After 12 weeks of experiment，the bone mineral density(BMD) and bone histomorphology of rats were observed，and the biochemical indexes of bone metabolism in serum of rats in each group were detected.The expressions of PPAR-gamma，Axin 2 and beta-catenin protein were detected by Western blotting.Results:After 12 weeks，BMD values of femur，pelvis，spine and whole body in model group were lower than those in isopsoralen group(P<0.05); serum Ca，P and TRACP levels in isopsoralen group were lower than those in model group，and serum ALP levels were higher than those in model group(P<0.05); bone histomorphometric analysis showed that the trabeculae of model group were sparse and fractured obviously.The percentage of bone trabecular area and the number of bone trabeculae increased significantly，and the degree of trabecular segregation decreased significantly(P<0.05).After 12 weeks，compared with model rats，PPAR-gamma and Axin 2 protein levels in isopsoralen group were down-regulated and beta-catenin protein expression was significantly increased(P<0.05).Conclusion:Isopsoralen may improve the abnormal bone metabolism in rats by inhibiting Axin2/PPAR gamma signaling pathway，activating Wnt signaling pathway and improving bone metabolism in rats.