Objective:To reveal the mechanism of Zuogui Pill (左归丸) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for expounding the scientific connotation of the kidney dominating the bones in TCM.Methods:Forty-two male Wistar rats were selected and randomly divided into three groups,control group (n=12),model group (n=15) and Zuogui Pill group (n=15).Form the beginning,The rats were injected dexamethasone for eight weeks to make the model of osteoporosis,and the Zuogui Pill were administered intragastrically to the rats of Zuogui Pill group for eight weeks.The relative morphological parameters were measured in the undecalcified tibial slices.And the protein expression levels of Wntl,LRP-5 and β-catenin in rat tibial osteoblasts (0B) and bone marrow stromal cells (BMC) were detected by immunohistochemistry.Results:Compared with the control group,TBV% and TFS% decreased significantly,while TRS% increased significantly,and the protein expression of Wntl,LRP-5 and β-catenin in OB and BMC decreased significantly in the model group.And compared with the model group,TBV% and TFS% increased significantly,and expression levels of Wntl,LRP-5 and β-catenin proteins increased significantly in the Zuogui pill group.Conclusion:Zuogui Pill can prevent and treat glucocorticoid-induced osteoporosis in rats by up-regulating the expression of the key signal molecules Wntl,LRP-5 and B-catenin in Wnt signal transduction pathway.