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Objective: To investigate the effects of carnosine on lipopolysaccharide (LPS)-induced inflammasome activation and pyroptosis in microglia, and to clarify its mechanism.Methods: Activation model of microglia was established by LPS (10 ng/ml) .CCK-8 assay was used to detect cell activity of microglia treated with different concentrations of carnosine (0.2, 1, 5, 20, 50 mmol/L) for 6 h, and the cell activity of microglia pretreated with different concentrations of carnosine for 0.5 h and then stimulated with LPS for 6 h, to screen a suitable concentration.Then microglia were divided into control group, carnosine group (5 mmol/L), LPS group, and LPS+carnosine group: cell morphological changes in each group were observed under an inverted phase contrast microscope; levels of IL-1β, TNF-α and IL-6 in microglial culture medium were measured by ELISA; propidium iodide (PI) staining was used to detect pyroptotic cells; immunofluorescence was used to observe protein expression of Nod-like receptor protein 3（NLRP3) .Results: Compared with control group, cell viability of microglia in LPS group was significantly decreased (P<0.01), the shape of microglia was mostly "amoeboid", levels of IL-1β, TNF-α and IL-6 in microglial culture medium were significantly increased (P<0.01), the positive rate of PI and the number of NLRP3 positive cells were significantly increased (P<0.01). Compared with LPS group, cell viability of microglia in LPS+carnosine group was significantly increased (P<0.01), the number of "amoeboid" microglia was decreased, levels of IL-1β, TNF-α in microglial culture medium were significantly decreased (P<0.01), and the level of IL-6 was decreased (P<0.05), the positive rate of PI and the number of NLRP3 positive cells were both significantly decreased (P<0.01). Conclusion: Carnosine can inhibit LPS-induced microglia activation and inflammasome activation, thereby inhibiting cell pyroptosis and the release of inflammatory factors. [ABSTRACT FROM AUTHOR]