Abstract: Objective To explore the influence of cyasterone on the osteoclast and osteoblast differentiation and then to investigate its effect on the bone quality in the osteoporosis mice. Me thods CCK8 assay was firstly used to detect the toxic effect of cyasterone on the mouse bone marrow derived mononuclear macrophages (BMMs) and anterior osteoblast lines MC3 T3 E1. Cell apoptosis was measured by flow cytometry. Then TRAP staining and ALP staining were employed to detect osteoclast differentiation and osteoblast differentiation, respectively. Realtime PCR was carried out to test the expression of osteoclast special gene TRAP and osteogenesis crucial gene ALP. In vivo, 15 mice were divided into three groups: sham-operated group, OVX group and OVX + cyasterone treatment group. In treatment group, cyasterone was used as 5 mg/kg every day. Sham-operated group and OVX group were treat with saline solution. After 4 weeks, the tibia was collected for Micro-CT detection to observe the bone quality and microstructure changes. Re s ults Cyasterone with the concentration of less than 10 mg/L had no significant cytotoxicity nor influence on the apoptosis (P >0.05) . Cyasterone could significantly inhibit the osteoclast differentiation of BMMs (P<0.05) , simultaneously, it also had the effect to promote the osteoblast differetiation of MC3 T3 E1. Real-time PCR indicated that cyasterone could block the expression of TRAP and increase the expression of ALP (P<0.05) . In vivo, cyasterone was able to obviously improve the osteoporosis status caused by estrogen deficiency without general toxicity. Conclus ion cyasterone could provide a good treatment for osteoporosis through the bidirectional effect of inhibiting osteoclast differetiation and promoting osteoblast differentiation.