Acute lung injuries (ALI) is a very common clinical disorder that triggers substantial health issues worldwide. An excessive inflammatory response is a vital feature of ALI, however the mechanism continues to be unclear, particularly the role of endoplasmic-reticulum (ER) stress and autophagy. To recognize cellular mechanism of lung inflammation during lipopolysaccharide (LPS)-caused mouse type of ALI, we investigated the influence of classic ER stress inhibitor 4-phenyl butyric acidity (4-PBA) on ER stress and autophagy, which partly modify the activation of inflammation, in LPS-caused ALI mouse model and human alveolar epithelial cell model. We shown that 4-PBA, which further avoided the activation from the NF-|¨ºB path, decreased the discharge from the pro-inflammatory mediators IL-1|?, TNF-|¨¢ and IL-6, considerably inhibited LPS-activated ER stress. Furthermore, it had been discovered that autophagy seemed to be decreased by treating 4-PBA, which might play a safety role in ALI models with the classical AKT/mTOR signaling path. Inhibition of autophagy by 3-MA exacerbates cytotoxicity caused by LPS in A549 alveolar epithelial cells. Taken together, our study established that ER stress is really a key promoter within the induction of inflammation by LPS, the protective aftereffect of 4-PBA relates to the inhibition of ER stress and autophagy in LPS-caused ALI models. In addition, the function of autophagy that includes to cell survival may rely on the activation of ER stress.