Inhaled leytragin, an agonist of the δ‐opioid receptor, is demonstrated to inhibit HMGB1 secretion in LPS‐induced ALI of mice by preventing hyperacetylation at lysine residues and promoting sirtuin 1 to deacetylate HMGB1.143. The gene discussed is HMGB1; the disease is acute respiratory distress syndrome.