Abstract: Abstract Purpose: Establish acute radiation-induced lung injury model in mice, and observe the protect effect of glycyrrhetinic acid on the model. Materials and Methods: 90 adult C57BL /6 female mice were randomly divided into three groups: (1) control group (Conrol group): no irradiation; (2) glycyrrhetinic group (GA group): irradiation + glycyrrhetinic acid 40mg/kg by gavage; (3) irradiation group (IR group): irradiation + saline 0.01ml/g by gavage. Irradiation groups were exposed to a single fraction of X-rays (12 Gy) to the thorax. Two days ,17 days and 30 days after irradiation, random 10 mice of every group were executed. Histopathological analyses of lung tissues were done with HE and Masson staining to assess lung injury. Results: The control group showed no obvious inflammatory changes. However, massive infiltration of inflammatory cells in alveolae and alveolar septal were observed in the IR group on day-2 and day-17. Whereas, alveolar septal thickening, alveolar structure deformation, the infiltration of inflammatory cells, and collagen fibers deposition were observed in the IR group on day-30. Histologic scoring demonstrated that GA administration mitigated alveolitis and collagen deposition significantly as compared with NS administration at each time point (P<0.05). Conclusions: Lungs of C57BL /6 mice irradiated with a single fraction of 12 Gy X-ray can build up an animal model of acute radiation-induced lung injury. Glycyrrhetinic acid can alleviate the inflammatory reaction and collagen deposition of acute radiation-induced lung injury phase.