Here, we evaluated the effects of raltegravir in vitro and in vivo using experimental models of lipopolysaccharide (LPS)-induced ALI, and we specifically examined the ability of this integrase inhibitor to prevent lung endothelial injury by suppressing NLRP3 activation and HMGB1/TLR4/NF-κB signaling in response to LPS treatment. The gene discussed is TLR4; the disease is acute respiratory distress syndrome.