Objective To explore the method of establishing a mouse model of levofloxacin resistance by infectionwith Pseudomonas aeruginosa (PA) in combination with a low-dose levofloxacin administration. Methods The model ofpneumonia was induced by infecting mice with a PA standard strain. Different concentrations of bacterial suspension, timesof infection and lerofloxacin administration method were analyzed. The therapeutic effect of levofloxacin was analyzed andthe feasibility of establishing the model was determined by measuring body weight changes and lung index of the mice.Results There were significant differences in lung indexes between the model groups 1 and 2 and normal group ( P <0. 01), and there was no significant difference between levofloxacin group 2 and model group 2 after single infection of PA(1×10⁹cfu/ mL) in mice treated with low-dose levofloxacin. In the experiment of single infection of PA (1×10¹⁰ cfu/ mL)plus low-dose levofloxacin,there were significant differences between the model groups 1 and 2 and the normal group ( P <0. 01), and there was no significant difference between levofloxacin group 3 and model group 2. Levofloxacin groups 1 and2 significantly reduced the lung index in model group. In the experiment of repeated infection of PA in mice,there weresignificant differences between model groups 1 and 2 and normal group ( P < 0. 01). There was no significant differencebetween the levofloxacin group 2 and model group 2. In each experiment, the body weight of mice in the experimentalgroups was lower than that of the normal group on the second day after infection, although this was not significantlydifferent. Conclusions Under the experimental conditions used in our study, this animal model can simulate thephenomenon of drug resistance to a certain extent generated by PA (1×10¹⁰ cfu/ ml) single infection and PA repetitive infection combined with administration of a low-dose levofloxacin.