Background and Objective: Lunar dust is a kind of fine particles exists on the surface of the moon and it has become one of the most important challenges in future space missions. Lunar dust is toxic but the understanding of lunar dust toxicity is very poor. The aim of this study was to investigate the acute lung injury induced by lunar soil simulant and the mechanism of toxicity. Materials and Methods: Wistar rats were randomly divided into four groups including saline control group (tracheal perfusion in a 1 mL volume), two Chinese Academy of Sciences-1(CAS-1) lunar soil simulant groups (tracheal perfusion with 7 and 0.7 mg, respectively in a 1 mL volume) and PM2.5 group (tracheal perfusion with 0.7 mg in a 1 mL volume). The levels of tumor necrosis factor alpha, interleukin 6, immunoglobulin A and immunoglobulin G in the bronchoalveolar lavage fluid were examined and the changes of malondialdehyde, glutathione peroxidase and superoxide dismutase in the lung tissue were later measured after 4 and 24 h. Results:The determination of the cytokines, immunoglobulin and the oxidative stress index in lung tissue showed that the significant immune and oxidative stress response in the respiratory system were caused by lunar soil simulant and the immune and oxidative stress response promoted each other, resulting in toxic effect on pulmonary parenchymal cells and membrane of rats. Conclusion: The overall results showed that the immune response and oxidative stress reaction induced by lunar soil simulant were significant in the respiratory system. They promote each other, so as to cause the toxic effects on the lung parenchyma cells and membrane tissues of rats.