Background: Asthma is a chronic airway inflammatory disease characterized by airway wall remodeling. The mechanisms underlying airway remodeling in asthma are not fully understood. There is an urgent need to investigate global protein profiling of chronically inflamed lungs to identify novel pathogenic molecules and biomarkers for chronic asthma. In this study, we described the first differentially expressed proteome of lung tissue and bronchoalveolar lavage fluid from a mouse chronic asthma model. Methods: BALB/c mice sensitized to ovalbumin were challenged with ovalbumin aerosol 3 times per week for 8 weeks. The lung tissue and lavage fluid proteins were resolved by 2-dimensional gel electrophoresis, and differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. Results: Airway goblet cell hyperplasia, smooth muscle hyperplasia, subepithelial fibrosis, airway hyperresponsiveness, pulmonary inflammatory cell infiltration and elevated serum ovalbumin-specific IgE level were observed in our chronic asthma model. We have identified at least 100 protein spots that were differentially expressed in chronically inflamed lungs, and the identity of 66 protein spots was confirmed. Conclusions: Many of these proteins, including cytoskeleton-related proteins, Ca2+-binding proteins and anti-oxidant proteins, may be related to the development of airway remodeling, and they should be evaluated further as potential therapeutic targets and biomarkers for chronic asthma.