Abstract: Objective To investigate the improving effect of modified Chaihu Guizhi Decoction (CGD) on osteoporosis rats by regulating the Wnt/ β-catenin signaling pathway. Methods SD rats were assigned to Model, CK, high-dose CGD (CGD-H; 20 g/ kg), low-dose CGD (CGD-L; 5 g/ kg), and estradiol valerate (EV; 9 mg/ kg), Wnt/ β- catenin pathway inhibitor (DKK-1, 100 mg/ kg), and CGD-H+DKK-1 (20 g/ kg+100 mg/ kg) groups with 12 rats per group. Except for those in the CK group, rats were administered 70 mg/ kg retinoic acid to establish the osteoporosis(OP) model, and rats in the CK group were administered the same amount of normal saline. From week 4 of modeling, the corresponding drug was administered for 4 weeks. ELISA were applied to measure serum levels of collagen type I C-terminal peptide (CTX-Ⅰ) and osteocalcin (BGP). Changes in the bone volume fraction, bone trabecular thickness, bone mineral density, and bone trabecular number were observed. HE staining was applied to assess pathological changes in the rat femur. Alkaline phosphatase (ALP) calcium-cobalt staining was applied to detect osteoblast activity in the rat femur. Osteoclast activity in rat femur tissue was detected by tartrate-resistant acid phosphatase (TRAP) staining. Western blot was applied to detect Wnt3a and β-catenin proteins in femoral tissue. Results Compared with the CK group, femoral tissue of the Model group had severe pathological damage, the CTX-Ⅰ level and osteoclast activity were increased, and the BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, and Wnt3a and β-catenin protein expression were decreased (P< 0. 05). Compared with the Model group, pathological damage of the femur in CGD-L, CGD-H, and EV groups was alleviated, the CTX-Ⅰ level and osteoclast activity were decreased, the BGP level, bone volume fraction, trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, and Wnt3a and β-catenin protein expression were increased, and the opposite trends of the corresponding indicators were observed in the DKK-1 group (P<0. 05). Compared with the CGD-H group, femoral tissue of the CGD-H+DKK-1 group was severely damaged, the CTX-Ⅰ level and osteoclast activity were increased, and the BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, and Wnt3a and β-catenin protein expression were decreased (P<0. 05). Conclusions CGD may improve OP in rats by activating the Wnt/ β-catenin pathway.