Objective To preliminarily explore the mechanism of the effect of the strong-bone decoction on osteoblast ( OB) differentiation by regulating osteoclast (OC), derived exosomes. Methods The serum containing of the strong-bone decoction was prepared and the differentiation models of OC and OB were constructed. The control-serum group and drug-serum group were set up. The best drug containing serum concentration for intervening the OC differentiation was discovered. The exosomes release was detected using Western blotting (WB) method . ALP contents were detected with chemiluminescence method . The expressions of runt,related transcription factor 2 ( Runx2), osteopontin ( OPN), and osteocalcin ( OCN) were measured with real-time PCR. Finally, the expression of ß-catenin in OC and OB was detected wit WB. Results The cell staining showed that the activity of TRAP was significantly inhibited in the drug-serum group. CD9, CD63, and CD81 were expressed in exosomes of OC differentiation model in both groups. The expressions of ALP, Runx2, OPN and OCN in both intervening groups were lower than those in the control group. However, these osteogenic factors expressed more in the drug-serum group than in the control-serum group. The expression of ß-catenin in OB in both groups was lower than that in the control group. However, ß-catenin in OB expressed more in the drug-serum group than in the control-serum group. ß-catenin in OC expressed more in the drug-serum group than in the control-serum group. Conclusion The strong-bone decoction inhibits the differentiation of OC and improves the negative effect of osteoclast-derived exosomes on OB differentiation. The osteoclast-derived exosomes may transfer miRNA to act on wnt / ß-catenin pathway and influence OB differentiation. [ABSTRACT FROM AUTHOR]