Therefore, in this study, we investigated the roles of sesamin in regulating the development of sepsis via the HMGB1/TLR4/IL-33 signalling pathway by examining its impacts on the production of pro-inflammatory cytokines and the expression of IL-33, HMGB1, TLR4, ZO-1, and occludin. The gene discussed is TJP1; the disease is Sepsis.