Objective To explore the possible mechanism of Zuogui Pills（左归丸） in the treatment of osteoporosis. Methods Sixty female Sprague-Dawley rats were randomly divided into control group

sham operation group

model group

western medicine group and Zuogui Pills group

with 12 rats in each. Rats in the model group

western medicine group

and Zuogui Pills group were subjected to bilateral oophorectomy to establish osteoporosis model. After modeling

Zuogui Pills group was given Zuogui Pills 0. 968 g/100 g gavage

and western medicine group was given 0. 018 mg/100 g gavage estradiol valerate tablets. Blank control group

sham operation group and model group were given purified water 1 ml/100 g gavage. Once a day

6 days in every week for 3 months. The lumbar vertebral bone density

femur maximum load

flexural strength

elastic modulus

iron ion levels and hepcidin protein expression in rat liver

osteoprotegerin（OPG） and receptor activator of nuclear factor kappa-Β ligand（RANKL） in tibia bone marrow were measured after medication finished. Results Compared with the sham operation group

the bone mineral density and femur maximum load

flexural strength

and elastic modulus of the lumbar vertebrae in the model group were decreased. The level of iron in the hepatic tissue was increased and Hepcidin protein was decreased. The expression of OPG protein in the tibia bone marrow was decreased

and RANKL protein expression increased（P < 0. 05 or P < 0. 01）. Compared with the model group

the lumbar bone mineral density and femur maximum load

flexural strength

and elastic modulus of the Zuogui Pills group and the western medicine group increased.The iron ion level in the liver tissue decreased

and Hepcidin protein expression increased. OPG protein expression in the tibia bone marrow was increased

and RANKL protein expression decreased（P < 0. 05 or P < 0. 01）. Conclusion Zuogui Pills can increase the level of Hepcidin secreted by the liver

then regulate the OPG/RANKL signaling pathway

ultimately reduce osteoclast activity

reduce bone loss and protect bone tissue. This may be one of the mechanism in treating osteoporosis.