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Chlorine gas (Cl ) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl -induced ARDS. ARDS was induced by Cl exposure in male C57BL/6 mice.