By detecting the expression, subcellular localization, and secretion of HMGB1; the production of TLR-4; the expression of NF‐κB signalling pathway-related proteins; and the intervention of SFI on these proteins in the lung tissues of endotoxin shock rats, we conclude that the effect of SFI on ALI induced by endotoxin shock at least partially depends on the inhibition of the HMGB1/TLR4/NF‐κB signalling pathway. Here, HMGB1 is linked to acute respiratory distress syndrome.