ObjectiveTo establish rabbit model of pulmonary Pseudomonas aeruginosa (PA) infection by two different methods and make evaluation and comparison from the pathology, imaging and other aspects. MethodsTotally 48 healthy New Zealand rabbits were randomly divided into 4 groups (n=12): group A, B, C and D. Group A was inoculated with PA suspension via percutaneous tracheal puncturing; Group B was inoculated with PA suspension via spraying inhaling; and group C and D were treated with sterile saline suspension serving as puncturing control and inhaling control, respectively. PA inoculation was done in the four groups every other day, and chest CT scan was performed every other day after inoculation. Pulmonary pathological examination was done after the death of the animals. The two methods were evaluated and compared concerning the pathological, imaging, and laboratory findings. Results(1) Pathological findings in group A and B: For animals of early death, there were pulmonary edema of different degrees, hemorrhage, nodule-like abscess, and consolidation; moreover, severe neutrophil infiltration and abscess-like lesions in lung tissue were observed under the microscope. For animals of later death, the consolidation was gradually relieved and the main pathological findings included local atelectasis, fibrosis, granuloma formation, and lymphocyte infiltration. (2) Radiographic findings in group A and B: Chest CT showed bilateral multiple patchy opacities, with consolidation and abscess seen in some areas. Lesions on CT were found at 5 days after inoculation in group A and at 7 days after inoculation in group B.ConclusionRepeatedly inoculating PA suspension via both percutaneous tracheal puncturing and spraying inhaling can successfully establish rabbit model of pulmonary PA infection, and each method has their own advantages in performance, controllability, and adaptability.