Background: MDSC(myeloid-derived suppressor cell) and M2 macrophage in tumor microenvironment are involved in tumor progression by inducing immune tolerance to cancer cells and tumor antigens. It has been reported that metformin has anti-in-fi ammatory and anti-tumor effects. However, there is no report about the effect of metformin on infi ammatory cells of tumor microenvironment and its mechanism. Methods: THP-1 cells were used, and treated with metformin 0.25, 0.5, 1, 2.5, 5 mM for 48 hrs. We performed fi ow cytometry analysis, utilizing surface markers such as CD33, arginase, CD206, CD163, and CD68, to estimate MDSC and M2 macrophagefraction of THP-1 cells. To investigate AMPK-mTOR and cholesterol pathway, we perfomed western blot analysis for p-AMPK and p-S6, and treated AICAR(AMPK activator), Compound C(AMPK inhibitor), rapamycinm(mTOR inhibitor), and mevalonate (mediator of cholesterol metabolism). Results: The treatment of metformin to THP-1 cells decreased the fraction of MDSC( CD33, arginase), and M2 macrophage(CD206, CD163). In western blot analysis,metformin treatment activated p-AMPK and inhibited p-S6. The fraction of MDSC and M2 macrophage was decreased by AICAR and increased by Compound C teatment. The inhibitory effect of metformin on MDSC and M2 macrophage was reversed by Compound C and mevalonate treatment. In addition, rapamycin treatment to THP-1 cells also decreased the fraction of MDSC and M2 macrophage, which was reversed bymevalonate treatment. Conclusion: The inhibitory effect of metformin on MDSC and M2 macrophage is mediated by activation of AMPK, and inhibition of mTOR and cholesterole metabolism pathway. Key words: metformin, MDSC, M2 macrophage, AMPK, mTOR