Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.