Objective To evaluate the effect of astaxanthin against radiation-induced lung fibrosis in mouse model and to investigate the underlying mechanism. Methods A total of 60 female C57BL/6 mice were evenly randomized into control group, model group (IR) and astaxanthin-treated group (IR+AST). Mouse models of radiation-induced lung fibrosis were generated by thoracic irradiation with a single dose of 16 Gy. Mice in IR+AST group were orally administrated with astaxanthin (25 mg/kg) daily for 7 days both before and after irradiation. Then the mice were sacrificed at 1, 4, 8 and 16 weeks after radiation, and the lung samples were collected in each group for morphological observation. The severity of fibrosis was evaluated by Masson's trichrome after radiation. The oxidative stress was determined by malondialdehyde (MDA) and superoxide dismutase (SOD) assay kit, the collagen deposition was measured by hydroxyproline (Hyp) assay kit, and the serum level of transforming growth factor-beta 1(TGF-β1) was measured by ELISA. Results Pathological staining results showed that the pulmonary fibrosis became more severe along with time increase after irradiation, and astaxanthin attenuated the fibrosis formation. Compared with irradiation model group, the MDA level in IR+AST group was significantly lower (P<0.05 or P<0.01) and SOD level was significantly higher (P<0.05 or P<0.01) at different time points. Radiation increased the serum TGF-β1 and Hyp content in lung tissue at 4, 8 and 16 weeks post irradiation, and astaxanthin significantly reduced TGF-β1 and Hyp contents (P<0.05 or P<0.01)). Conclusion Astaxanthin can effectively alleviate radiation-induced lung fibrosis (RILF), which is probably via inhibition of TGF-β1 expression and reduction of lipid peroxidation injury.