Objectives: Stenotrophomonas maltophilia causes severe hemorrhagic pneumonia with a reported mortality rate of 100%. However, currently there are no available mouse models of hemorrhagic pneumonia. In the present study, we generated a mouse model of hemorrhagic pneumonia and subjected the animals to treatment with levofloxacin and moxifloxacin to determine if this model can be used to determine therapeutic effects. Methods: S. maltophilia was transtracheally administered to mice immunosuppressed with cyclophosphamide. We confirmed its pathological status and assessed whether therapeutic effects of quinolone antibiotics could be studied using the model. Levofloxacin and moxifloxacin were then administered to evaluate survival rate, bacterial load in the lungs and cardiac blood, as well as pathological changes in diseased lungs compared with those of the control group. Results: Hemorrhagic pneumonia developed within 16–24 h after bacterial infection and was confirmed pathologically. Levofloxacin and moxifloxacin significantly improved survival rates, decreased the bacterial load in lungs and cardiac blood, and improved hemorrhagic pneumonia as indicated by pathological examination. Conclusions: We established a mouse model of rapidly progressive fatal hemorrhagic pneumonia caused by Stenotrophomonas maltophilia which is useful for determining the therapeutic effect of various agents. We believe that this model will prove useful to further elucidate the mechanisms underlying hemorrhagic pneumonia, as well as in the design and development of novel therapeutic modalities and targets.