We investigated the expression and function of matrix metalloproteinase-12 (MMP-12) in a model of allergic airway inflammation. Mice were sensitized mucosally by exposure to aerosolized ovalbumin (OVA) daily over a period of ten days in the context of adenovirus-mediated GM-CSF expression. The ensuing inflammatory response is characterized by a Th2 cytokine profile, OVA-specific IgE and airway eosinophilia. Using real-time, quantitative RT-PCR (TaqMan), we assessed MMP-12 mRNA expression in whole lung tissue. We observed a 12- and 70-fold increase in expression at days 7 and 11, respectively, in OVA-exposed mice when compared to naive controls. Immunoblot analysis revealed an increase in MMP-12 protein in the bronchoalveolar lavage fluid (BAL) of mice exposed to OVA in the context of GM-CSF. No such elevation was observed in mice exposed to saline only in the context of GM-CSF. To assess functional role of MMP-12, MMP-12 knockout (KO) mice were subjected to the aforementioned protocol. We observed an 80% reduction in eosinophils in the BAL of KO mice compared to their wildtype (WT) littermates. Using IL-13 KO mice, we demonstrated that expression of MMP-12 is IL-13-dependent. Collectively, our data indicate a novel function for MMP-12 in the process of airway eosinophil accumulation.