Abstract: Objective To interpret new molecular targets for breast cancer therapy and investigated the molecular mechanism of alternatively activaed macrophages(M2)′s promotion in breast cancer invasion and migration. Methods Mononuclear cells were isolated from peripheral blood of normal adults by density gradient centrifugation,and alternatively activated M2 in vitro.Activation of M2 to breast cancer signal molecules was detected by Western blot.The inhibition function of PI3K/ERK inhibitors to (M2)′s promotion in breast cancer migration was evaluated by invasion assay and wound assay. Results To simulate breast cancer microenvironment,we co-cultured M2 and breast cancer MDA-MB-231 cells.In the co-cultur system,the inhibitors,LY294002 of PI3K,U0126 of MEK, inhibiting (M2)′s activation to breast cancer PI3K/ERK in 6,12 h.The two inhibitors can prevent (M2) from promoting breast cancer invasion and migration. Conclusion The inhibitors of PI3K/MEK prevent M2 from promoting breast cancer invasion and migration.They can be new targets of breast cancer therapy.