Objective: The medicinal importance of Glycyrrhiza glabra is well reported in Asian folk core medicine. In the current study, we have investigated the treatment effects of ethanolic extract of G. glabra in acute lung injury (ALI) mice models. Materials and Methods: ALI murine models were established by intratracheal instillation of bacterial lipopolysaccharide (LPS). Bronchoalveolar lavage fluid (BALF) was prepared for measuring cell migration and cell count, protein content, and superoxidase dismutase (SOD) activity. Lung tissues were collected for evaluating the wet-to-dry weight ratio, messenger ribonucleic acid (mRNA) expression of pro-inflammatory cytokine, and histological change. Results: It was observed that the treatment of ALI mice significantly decreased the total cell count and exudation of protein into BALF. Further, SOD activity in BALF of LPS-induced ALI mice was greatly improved when treated with G. glabra extract at 200 or 400 mg/kg of body weight, and the SOD activity increased in a dose-response manner. Evaluation of lung wet-to-dry weight ratio, pro-inflammatory mRNA expression levels, and histologic examination of lung tissues indicates that plant extract has significantly attenuated the tissue injury. Conclusions: The results showed that G. glabra had a protective effect on LPS-induced ALI in mice which might be contributed due to diverse phytoconstituents of the plant extract. To fulfill the unmet needs of treating ALI, the active principles in G. glabra could be promising lead-alternative therapy to develop high-potent anti-inflammation agents for ALI.