We have previously reported that obese db/db mice exhibit innate airway hyperresponsiveness. These mice also have enhanced inflammatory responses to ozone, a common air pollutant that exacerbates asthma. Since db/db mice are diabetic as well as obese, the purpose of this study was to determine whether metformin, an anti-hyperglycemic agent, alters the pulmonary phenotype of db/db mice. Lean wildtype (C57BL/6J) and obese db/db mice were treated by gavage with water or metformin (300 ug/g) once a day for 2 weeks. Twenty four hours after the last treatment, in mice of both genotypes, we either measured airway responsiveness to methacholine by forced oscillation, or we exposed the mice to ozone (2ppm for 3 h) and examined the ensuing inflammatory response. Compared to water, treatment with metformin caused a significant decrease in fasting blood glucose in obese mice. Airway responsiveness was increased in db/db versus wildtype mice, but metformin did not affect responsiveness in either group. Four hours after exposure to ozone, there was a significant increase in bronchoalveolar lavage fluid neutrophils and chemokines in mice of both genotypes, but the magnitude of these changes was greater in db/db than wildtype mice. Metformin did not affect ozone-induced inflammation in mice of either genotype. The results indicate that hyperglycemia is unlikely to account for the pulmonary phenotype of obese mice.