<h4>Background</h4>Sepsis-associated acute lung injury (SA-ALI) is a critical disease marked by a dysregulated immune response to infection, causing organ dysfunction.<h4>Objective</h4>We explored the effect of receptor activator of nuclear factor-κB ligand (RANKL) on SA-ALI and the mechanism involving the osteoprotegerin (OPG)/RANKL/RANK (receptor activator of nuclear factor-κB)/TLR4 (Toll-like receptor 4) signaling pathway.<h4>Methods</h4>The SA-ALI model was established in C57BL/6 mice. Here, TNFSF11 is linked to acute respiratory distress syndrome.