Objective To establish an inhalation infection pneumonia model of C57BL/6J mice with highly virulent and multi-drug resistant Pseudomonas aeruginosa(PA)strain F291007,and to study the microbiological,pathological and immunological characteristics of this model.Methods The strain F291007 was isolated and identified before the bacterial suspension was administered to the mice via aerosolized intratracheal inoculation to establish the pneumonia infection model.In the course of infection,the conditions and survival of the mice were observed,and the bacterial loads,the histopathological states and the cytokine expression levels in the major organs were detected.Finally,three key cytokines were blocked to observe the survival of mice.Results The strain F291007 was isolated and identified.After lethal dose infection,all the mice died within 24 h.After sub-lethal dose infection,a large number of immune cells in the body were capable of phagocytosis and killing of invading pathogens,which was manifested as rapid clearance of bacteria in lungs and the exponential decrease of bacterial load with the passage of time.The pathological changes in lungs were most severe at 1 to 3 days but gradually recovered.After infection,interleukin-6(IL-6),IL-17A and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid and serum were significantly increased at 1 to 3 days.After blocking of these three cytokines with specific antibodies,the survival rates of infected mice decreased significantly.Conclusion A mouse model of gradually-recovered pneumonia infection caused by PA inhalation has been established,suggesting that the first one to three days are critical to immune response after infection through multiple indicators.This mouse model can be used for research on the pathogenesis,immunoregulation and treatment evaluation of highly virulent and multi-drug resistant PA inhalation pneumonia infection.