Objective To study the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury (ALI) induced by oleic acid (OA).Methods Seventy-two male Sprague Dawley (SD) rats were equally divided into control group (C group),oleic acid-induced ALI group (OA group),oleic acid-induced ALI with sodium hydrosulfide (NaHS) pretreatment group (OA + NaHS group) and sodium hydrosulfide treatment group (NaHS group).The model of acute lung injury was made by oleic acid intravenous injection in dose of 0.1 mL/kg.NaHS was injected intra-abdominally in dose of 1 ml/kg with concentration of 56 μmol/L 30 min before administration of oleic acid for pretreatment.In control groups,saline was used instead of oleic acid and NaHS in the equivalent volume.Six rats of each group were sacrificed at 2 h,4 h and 6 hours separately after modeling for observing the acute injury of lung tissue.Index of quantitative assessment of histological lung injury (IQA),wet/dry weight ratio (W/D) and H2S level of lung tissues were measured.The endoplasmic reticulum stress markers included glucose-regulated protein 78 (GRP78) and α-subunit of eukaryotic translation initiation factor-2 (elF2α) in lung tissues were measured by immunohistochemical staining and Western blot.Results At the three observation intervals,the IQA score and W/D ratio of lung tissues significantly increased in rats-after OA injected,but significantly decreased in other rats receiving both OA and NaHS.At the three intervals,the level of H2S in lung tissue significantly decreased in rats after OA injected,but significantly increased in other rats receiving both OA and NaHS.GRP78 and elF2α decreased in rats after OA injected,but increased in other rats receiving both OA and NaHS especially at 4 h and 6 h after modeling.Conclusions The findings suggested that H2S could promote the response to alveolar epithelial cell endoplasmic reticulum stress in rats with ALI resulting in attenuating the damage of lung tissue caused by oleic acid.