In the pulmonary system, the binding of extracellular HMGB1 to its receptor for advanced glycation end products (RAGE) activates the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, leading to the upregulation of HMGB1 and other proinflammatory mediators and promoting the development of ARDS. This evidence concerns the gene HMGB1 and acute respiratory distress syndrome.