Herein, elevated levels of IRE-1, XBP-1S, Caspase-12, CHOP as well as the ratio of XBP-1S/XBP-1 U in lung tissues of ALI rats and LPS-stimulated BEAS-2B cells were reversed following DEX therapy, suggesting that DEX could alleviate LPS-induced ALI in vivo and in vitro by suppressing ERS. Here, CASP12 is linked to acute respiratory distress syndrome.