More severe forms of ALI may progress to acute respiratory distress syndrome, or ARDS. Autophagy has been shown to play a critical role in regulating the outcome of ARDS [120]. The clinical manifestations of ARDS are very severe and may lead to rapid lung function decline and death. Using one of most widely used murine models of ALI, the CLP, a recent study demonstrated that autophagy induction by rapamycin was able to improve the survival rate, histological scores, lung wet/dry ratios, PaO2/FiO2, and inflammatory cytokine and myeloperoxidase (MPO) levels in BALF, suggesting a protective role of autophagy in sepsis-induced ALI/ARDS [120]. In another study, the potential of BML-111, a lipoxin A4 receptor antagonist, was evaluated in controlling LPS-induced septic ALI/ARDS in rats. The authors showed that BML-111 inhibited apoptosis and induced autophagy in alveolar macrophages, in response to the LPS challenge, via the suppression of MAPK1 and MAPK8 signaling and was independent of mTOR [132]. Moreover, BML-111 controlled the LPS-induced production of pro-inflammatory cytokines, and reduced apoptosis in the rat lungs, and thus warrants further investigation in ALI/ARDS [132]. Mechanical ventilation (MV)-induced lung injury is another severe form of ARDS, wherein the activation of inflammasome has been shown to mediate ALI symptoms. In a recent article, starvation-induced autophagy augmentation was shown to protect against LPS- and MV-induced ARDS features by reducing IL-1β levels, decreasing lung permeability, and improving arterial oxygenation [133]. Thus, autophagy had a protective role in controlling the inflammasome activation and resolution of the MV-induced production of IL-1β, which plays a pathogenic role through inducing hypoxemia and increasing lung permeability in LPS/MV-induced ALI/ARDS [133]. Although some contrasting reports regarding the role of autophagy in ALI/ARDS were initially reported [134], there has been a consensus on the therapeutic advantage of autophagy augmentation in ALI/ARDS based on significant validation studies [64,120,122]. Thus, proper autophagy function is essential in attenuating the severity of ARDS in patients.