M. pneumoniae (Mp) has been linked to chronic asthma. Airway remodeling (e.g., airway collagen deposition or fibrosis) is one of the pathological features of chronic asthma. However, the effects of respiratory Mp infection on airway fibrosis in asthma remain unclear. In the present study, we hypothesized that respiratory Mp infection may increase the airway collagen deposition in a murine model of allergic airway inflammation in part through up-regulation of transforming growth factor beta-1 (TGF-1). Double (two weeks apart) inoculations of Mp or saline (control) were given to mice with or without previous allergen (ovalbumin) challenges. On days 14 and 42 after the last Mp or saline, lung tissue and BAL fluid were collected for analyses of collagen and TGF-1 at protein and mRNA levels. In allergen naive mice, Mp did not alter airway wall collagen. In allergen challenged mice, Mp infections did not change airway wall collagen deposition on day 14, but increased the airway collagen on day 42 which was accompanied by increased TGF-1 protein in the airway wall and reduced TGF-1 protein release from the lung tissue into bronchoalveolar lavage fluid. Our results suggest that Mp infections could modulate airway collagen deposition in a murine model of allergic airway inflammation with TGF-1 involved in the collagen deposition process.