Objective：To explore the effect and mechanism of macrophage scavenger receptor 1（MSR1）on osteogenic differentiation of bone marrow mesenchymal stem cells（BMSCs）. Methods：In vivo，MSR1 wild type（WT）and knock out（KO）mice were used to perform tibial monocortical defect model. Further，the three-dimensional reconstruction and parameter analysis after micro-CT scan were carried out on day 10 post-injury. In vitro，BMSCs were first stimulated by conditioned medium from MSR1 WT or KO primary macrophages. Then，CCK-8，Transwell，alizarin red staining，alkaline phosphatase staining and real-time quantitative reverse transcription polymerase chain reaction were performed to explore the effect of MSR1 on proliferation，migration and osteogenic differentiation of BMSCs. Western blot and ELISA were used to investigate the specific mechanism of MSR1 on osteogenic differentiation of BMSCs. Results：The loss of MSR1 significantly reduced the ability of bone regeneration in vivo. In addition，knockout of MSR1 in macrophages significantly affected the osteogenic differentiation ability of BMSCs，but not the proliferation and migration ability in vitro. We also identified MSR1 could increase the secretion of bone morphogenetic protein 2（BMP2）through JAK/STAT3 signaling pathway，thus exerting its regulatory effect on BMSCs osteogenic differentiation. Conclusion：MSR1 is one of the key molecules that macrophages play a role in regulating osteogenic differentiation of BMSCs，which provides a solid theoretical basis for targeting macrophages MSR1 to promote bone healing in the future.