OBJECTIVE: To investigate the effects of Qingre Jianpi decoction(清热健脾汤,QRJPD) on dextran sulfate sodium(DSS)-induced colitis mice and explore its mechanism.METHODS: All mice were randomly divided into six groups. Weight changes, disease activity index values, and histological damage were detected. Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays(ELISA) and immunohistochemistry(IHC) method. The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3(NLRP3) inflammasome were detected by western blot analysis, IHC, and quantitative reverse transcription polymerase chain reaction.RESULTS: QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis(UC), reduced the secretion of inflammatory cytokines, and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome.CONCLUSION: QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.