Objective:This study aims to investigate the effects and potential mechanisms of metformin on the inflammatory cytokine interferon (IFN)-γ induced cell damage in human ovarian granulosa cells KGN. Methods:The effects of metformin alone and with IFN-γ on the viability of KGN cells were detected using CCK-8 kit,and the cell growth status of KGN cells were observed under microscope. The apoptotic cells and the cell cycle in KGN cells were analyzed using flow cytometry. The mRNA expression levels of cyclin dependent kinase inhibitor 1A(CDKN1A),a gene related to cell cycle regulation,were analyzed using q-PCR. Results:IFN-γ treatment inhibited the vitality of KGN cells through blocking these cells from G0-G1 phase to S phase and promoting into apoptosis. Although metformin treatment alone had no obvious effects on the KGN cells, it alleviated the apoptosis in KGN cells and reversed the cell cycle which induced by IFN-γ. Moreover,metformin significantly inhibited the expression levels of CDKN1A in IFN-γ treated KGN cells. Conclusion:Metformin had a protective role on the IFN-γ induced cell injury in KGN cells by down-regulating the abnormal expression of the negative cell cycle regulator CDKN1A in these cells.