Abstract <p>M2-polarized microglial phenotype has been demonstrated to exert a pro-tumor immune response. However, its underlying mechanism in the development and growth of glioma remains unclear. Here, we studied the regulation and mechanism of colony stimulating factor 1 receptor (CSF-1R)/c-Myc axis on microglial polarization, as well as the proliferation of glioma cells. In this study, the abundance of CSF-1R was boosted in glioma tissues, and level of CSF-1R was connected with the prognosis of patients with glioma. Lack of CSF-1R expression abridged M2 polarization in microglia. Besides, repression of CSF-1R expression blocked the promotive effect of M2 microglia on proliferation of glioma cells. In addition, c-Myc knockdown could neutralize the effect of CSF-1R overexpression on microglial polarization and proliferation of glioma cells. The CSF-1R/c-Myc axis could stimulate secretion of pro-tumoral factors by M2 microglia. Downregulation of CSF-1R restrained the promoting effect of M2 microglia on the proliferation of glioma cells in vivo. In conclusion, these data suggested that CSF-1R/c-Myc axis promoted microglial M2 phenotype to boost proliferation of glioma cells, which further deepens our understanding on the role of microglia-associated tumor microenvironment in tumorigenesis of glioma.</p>