Abstract: 【Objective】The objective of this study was to analyze the inhibition mechanisms of mangiferin on lipopolysaccharide（LPS）-induced inflammatory response，with the goal of identifying a potential therapeutic agent for sepsis. 【Method】In this research，mouse alveolar macrophage（MH-S）were chosen as the subject of investigation，and the cytotoxic impact of mangiferin on MH-S was assessed using the CCK-8 assay. According to the cytotoxicity test，the concentration of mangiferin was 100 μg/mL. With normal cultured MH-S as the control，10 μg/mL LPS was used for 24 h to construct an in vitro inflammatory model（LPS group），and then 100 μg/mL mangiferin was intervened for 24 h（intervention group）. The contents of inflammatory factors（IL-1β，TNF-α，IL-6 and IL-18）in MH-S supernatants were measured by ELISA，gene expression of IL-1β，TNF-α，IL-6 and IL-18 was assessed using real-time fluorescence quantitative PCR， and changes in TLR4/NF-κB signaling pathway were measured by Western blotting and immunofluorescence.【Result】 Mangiferin did not have obvious toxic effect on MH-S when its concentration was below 287.60 μg/mL. Compared with the control group，the relative expression of IL-1β，TNF-α，IL-6 and IL-18 was extremely significantly increased in the LPS group（P<0.01，the same below），and the contents of IL-1β，TNF-α，IL-6 and IL-18 in the cell supernatant was significantly（P<0.05，the same below）or extremely significantly increased. Following treatment with mangiferin intervention，there was significant decrease in both relative expression levels of IL-1β，TNF-α，IL-6 and IL-18 genes and their secretion levels，suggesting that mangiferin could alleviate inflammatory response in MH-S induced by LPS. In addition， relative expression of NF-κB gene and protein expression level in MH-S of LPS group were extremely significantly higher than that of the control group，and the relative expression of NF-κB gene and protein expression level decreased significantly after mangiferin intervention，indicating that mangiferin could effectively inhibit expression of nuclear transcription factors in MH-S induced by LPS；the TLR 4 expression level on the surface of MH-S of LPS group was greatly increased，but the TLR 4 expression level on MH-S surface decreased greatly after mangiferin intervention，indicating that mangiferin could effectively inhibit TLR 4 expression on the surface of MH-S induced by LPS.【Conclusion】Mangiferin has no obvious inhibitory effect on the proliferation of MH-S cells，and the half proliferation inhibition rate（IC₅₀）of mangiferin is 287.60 μg/mL. Mangiferin has fine protective effect against the LPS-induced inflammatory response in MH-S， and the mechanism of action may be related to the reduction of inflammatory factor secretion by inhibiting the activation of TLR4/NF-κB signaling pathway.