The experiment was conducted to examine the effect of a high fat diet (HFD) on airway hyperresponsiveness (AHR) in mice. Twenty-three adult male C57BL/6 J mice were fed with HFD or regular chow diet for two weeks. The total respiratory resistance was measured by forced oscillation technique at baseline and after methacholine aerosol challenge at 1, 3, 10 and 30 mg/mL. Bronchoalveolar lavage (BAL) was performed. Lipid levels and lipid peroxidation in lung tissue were measured along with gene expression of multiple cytokines. Lungs were digested, and IL-1β secretion by pulmonary macrophages was determined. HFD feeding resulted in 11% higher body weight compared to chow. HFD did not affect respiratory resistance at baseline, but significantly augmented airway responses to methacholine compared to chow diet (40.5 ± 17.7% increase at 30 mg/ml methacholine, p < 0.05). HFD induced a 3.2 ± 0.6 fold increase in IL-1β gene expression (p < 0.001) and a 38 fold increase in IL-1β secretion in the lungs. There was no change in BAL and no change in any other cytokines, lipid levels or lipid peroxidation. Hence, HFD induced AHR in mice prior to the development of significant obesity which was associated with up-regulation of pulmonary IL-1β.