Objective: To investigate the improvement effect of modified Chaihu Guizhi Decoction (CGD) on osteoporosis rats by regulating the Wnt/β-catenin signaling pathway. Methods: SD rats were separated into CK group, Model group, low-dose CGD group (CGD-L group, 5 g/kg), high-dose CGD group (CGD-H group, 20 g/kg), and estradiol valerate group (EV group, 9 mg/kg), DKK-1 (Wnt/β-catenin pathway inhibitor) group (100 mg/kg), and CGD-H DKK-1 group (20 g/kg 100 mg/kg), 12 per group. Except for the CK group, the rats in other groups were given 70 mg/kg retinoic acid to build the OP rat model, and the rats in the CK group were given the same amount of normal saline. From the 4th week of modeling, the corresponding drug intervention was given for 4 weeks. ELISA was applied to detect the levels of collagen type I C-terminal peptide (CTX-Ⅰ) and osteocalcin (BGP) in serum of rats; the changes of bone volume fraction, bone trabecular thickness, bone mineral density and bone trabecular number were observed; HE staining was applied to detect the pathological changes of rat femur; Alkaline phosphatase (ALP) calcium-cobalt staining was applied to detect osteoblast activity in rat femur; the activity of osteoclasts in rat femur tissue was detected by tartrate-resistant acid phosphatase (TRAP) staining; Western blot was applied to detect Wnt and β-catenin proteins in femoral tissue of rats in each group. Results: Compared with the CK group, the femoral tissue of the Model group had severe pathological damage, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05); compared with the Model group, the pathological damage of the femur in the CGD-L group, the CGD-H group and the EV group was alleviated, CTX-I level and osteoclast activity decreased, BGP level, bone volume fraction, trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression increased, the trends of the corresponding indicators in the DKK-1 group were opposite to the above (P<0.05); compared with the CGD-H group, the femoral tissue of the CGD-H DKK-1 group was severely damaged, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05). Conclusion: CGD may improve OP of rats by activating the Wnt/β-Catenin pathway.