Objective A feasible and stable mouse model of thoracic aortic dissection ( TAD) combined with acute lung injury (ALI) was established using β-aminopropionitrile monofumarate (BAPN) 1 g / ( kg·d) administered in drinking water. The mouse model of TAD combined with acute lung injury (ALI) was established to provide a rational animal model to study TAD combined with ALI. Methods Forty-five SPF-grade 3-week-old C57BL/ 6J male mice were selected and randomly allocated to a CON group (normal dietary water; 15 mice) or BAPN group (administration in sterile water at 1 g / (kg·d); 30 mice) for 4 weeks. During the experimental period, the general condition and modeling rate of mice were observed. TAD model mice were validated, and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues. HE pathological staining, the wet /dry weight (W/ D) ratio, total protein level in bronchioalveolar lavage fluid (BALF), and interleukin(IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in BALF) were used to validate the TAD combined ALI model in mice. Results BAPN treatment significantly delayed the increase in body mass and water intake of mice. Compared with CON and non-TAD groups, the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened (P< 0. 05). HE staining of the aorta showed significant thickening of the middle aortic layer, and the structure of the aortic wall was damaged and disordered. HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen, alveolar wall epithelial exfoliation and hyaline membrane formation, and a significant increase in the pathological scores of lung injury (P< 0. 05). Total protein levels and expression of IL-1β,IL-6, and TNF-α in lung tissue, W/ D ratio, and BALF were also significantly increased ( P< 0. 05), whereas no significant difference was observed in the above indexes between the other two groups. Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.