Objective To establish and systematically evaluate a mouse chronic pulmonary Pseudomonas aeruginosa (PA) infection model, providing a reliable method for establishing a model for drug treatment of chronic PA infections. Methods A feasible modified method was used to prepare PA-coated alginate microbeads. A chronic PA infection model was established in C57BL / 6J mice using tracheal intubation instillation. Model success was systematically evaluated by observing changes in physiological state, blood routine analysis, bacterial load measurements in bronchoalveolar lavage fluid ( BALF) and lung tissue, measurement of inflammatory cytokine expression, and histopathological section analysis. Results After intratracheal instillation of alginate microbeads coated with PA, the infected mice showed poorer physiological condition and higher mass loss compared with mice in the normal and the saline-alginate microbead groups. PA was cultured from model mouse lung tissue homogenate and BALF, and the number of white cells and neutrophils in the blood significantly increased (P<0. 05). Additionally,levels of the pro-inflammatory cytokines tumor necrosis factor-α( TNF-α) and procalcitonin( PCA) in BALF were significantly elevated. Hematoxylin-eosin ( HE) and Masson staining of lung tissue pathological sections revealed significant inflammatory cell infiltration and pathological changes in the model group. Conclusions PA-coated alginate microbeads were successfully prepared using a modified method, and a chronic pulmonary PA infection model was established in mice through tracheal intubation instillation, providing a practical and feasible experimental animal model for PA infection drug treatment research.