To establish an in vitro model of microenvironment before lung metastasis，and explore the efficacy of S1pr1-stat3 signaling pathway in the mature process and at the same time to verify the intervention effect of Shuangshen Granule (SSG) on the model，and explore its potential mechanism.Methods:Mouse Lewis lung cancer cells and primary bone marrow cells were co cultured in vitro and the differentiation of bone marrow cells were intervened by s1pr1 activator Sew2871.The expression of MMP9，LOX，Version and Fibronectin，and the differentiation of MDSCs cells of the model were observed and the intervention effect of SSG on the model were detected.Results:S1pr1 could significantly promote the construction of the in vitro model of microenvironment before lung metastasis，and S1pr1-stat3 was the key signal pathway for the maturation of the model.SSG not only significantly reduced the expression of the signal pathway related proteins in the model，but also inhibited the expression of key proteins in microenvironment maturation，and significantly reduced the differentiation of bone marrow cells to MDSCs under the effect of signal pathway (P<0.05).Meanwhile，it also significantly inhibited some tumor-derived cytokines such as GM-CSF and TGF-β in the pre metastasis model (P<0.05).Conclusion:Shuangshen Granule can inhibit the maturation of the pre-lung metastasis microenvironment model before lung metastasis by inhibiting the expression of s1pr1-stat3 signal pathway and some tumor-derived cytokines.