【Abstract】Objective A feasible and stable mouse model of thoracic aortic dissection (TAD) combined with acute lung injury (ALI) was constructed using β-aminopropionitrile monfumarate (BAPN,1g/kg/d) administered by drinking water. The mouse model of TAD combined with acute lung injury (ALI) was constructed to provide a rational platform for the study of TAD combined with ALI. Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly divided into 15 mice in the CON group (normal dietary water) and 30 mice in the BAPN group (drinking water administration with sterile water configured as a solution of 1 g/kg/d) for 4 weeks. During the experimental period, the general condition and modeling rate of mice in the two groups were observed, and the TAD model of mice was validated and the BAPN group was divided into TAD and Non-TAD groups by measuring the maximum diameter of the ascending aorta and H&E staining of the aortic tissues of the mice. The pathological staining of H&E, wet/dry weight ratio (W/D) and total protein level in alveolar lavage fluid (BALF), and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression in the alveolar lavage fluid (BALF) to validate the TAD combined ALI model of mouse. Results BAPN intervention significantly delayed the increase in body mass and water intake in mice. Compared with the CON and Non-TAD groups, the maximum diameter of the ascending aorta of mice in the TAD group was significantly thickened (P < 0.05), H&E staining of the aorta showed significant thickening of the aortic wall, reduction in the number of smooth muscle cells, and fracture and disorder of elastic fibers, and H&E staining of the lung tissues showed significant interstitial edema and inflammatory exudation accompanied by thickening of the alveolar wall and enlargement of alveolar lumen, and a significant increase in the pathological scores of lung injury (P < 0.05), and total protein level and expression of IL-1β, IL-6, and TNF-α in lung tissue W/D and BALF were also significantly increased (P < 0.05), while there was no significant difference in the above indexes between the other two groups. Conclusion A mouse model of thoracic aortic dissection combined with acute lung injury can be successfully established by BAPN drinking water administration.