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RATIONALE: We have shown that obesity-associated attenuation of murine acute lung injury is driven, in part, by blunted neutrophil chemotaxis; yet, differences were noted between the two obesity models studied. We hypothesized that obesity-associated impairment of multiple neutrophil functions contributes to increased risk for respiratory infection, but that such impairments may vary between murine models of obesity. METHODS: We examined the most commonly used murine obesity models (diet-induced(DIO), db/db, CPEfat/fat, and ob/ob) using a K.pneumoniae pneumonia model and LPS-induced pneumonitis. Marrow-derived neutrophils from uninjured lean and obese mice were examined for in vitro functional responses. RESULTS: All obesity models showed impaired clearance of K. pneumoniae, but in differing temporal patterns. Failure to contain infection in obese mice was seen in the db/db model at both 24 and 48h, yet this defect was only evident at 24h in CPEfat/fat and ob/ob models, and at 48h in DIO. LPS-induced airspace neutrophilia was decreased in all models, and associated with blood neutropenia in the ob/ob model, but leukocytosis in the others. Obese mouse neutrophils from all models demonstrated impaired chemotaxis, whereas G-CSF-mediated survival, LPS-induced cytokine-transcription, and MAPK and STAT3 activation, were variably impaired across the four models. CONCLUSIONS: Obesity-associated impairment of host response to lung infection is characterized by defects in neutrophil recruitment and survival. Yet, critical differences exist between commonly used mouse models of obesity, and may reflect variable penetrance of elements of the metabolic syndrome and other factors.