Objective To explore the role of high mobility group B1 （HMGB1） protein in the post-traumatic endoplasmic reticulum stress （ERS） in rat lung tissues. Methods The rat model of acute lung injury was established by crushing the hind limbs of rats with standard weight. The first experiment was to divide rats into postural control group and crush groups （6 h, 18 h and 30 h after crushing）. The second experiment was to divide rats into postural control group, 18 h crush group, HMGB1 inhibitor sodium butyrate （SB） group and 18 h crush+SB group. The protein expression changes of HMGB1 and ERS- related proteins （GRP78, caspase-12, CHOP and IRE1α） in rat lung tissues were detected with Western blotting. Meanwhile, the pathological changes of rat lungs were observed by HE stain. Results Compared with the postural control group, the expression levels of ERS-related proteins （GRP78, caspase-12, CHOP and IRE1α） and HMGB1 protein in rat lung tissues by crushing the hind limbs of rats were obviously increased. The protein levels reduced at 30 h after crushing but were still higher than those of postural control group and obvious pathological changes of acute lung injury were observed simultaneously in rats. Compared with the 18 h crush group, the expression levels of the ERS-related proteins and HMGB1 protein in rat lung tissues were attenuated in 18 h crush+SB group, and the pathological changes of rat lung injury began to alleviate. Conclusion HMGB1-ERS pathway activated by traumatic stress can lead to acute lung injury in rats.