Acute exposure to ozone (O₃), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines, including interleukin (IL)-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], tumor necrosis factor (TNF) receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β), promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin, yet given the aforementioned observations, we hypothesized that murine resistin promotes O₃-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indices of O₃-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O₃. In wild-type mice, O₃ increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O₃ increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient as compared to wild-type mice, no genotype-related differences in the other indices existed following O₃ exposure. O₃ caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were non-existent subsequent to O₃ exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O₃ exposure but does not promote O₃-induced lung pathology.