High levels of particulate pollution are becoming commonplace worldwide. For those with respiratory symptoms, greater air pollution levels can exacerbate respiratory disease. One possible driver of the enhanced asthmatic responses upon fine particulate matter (PM2.5) exposure is the activation of dual oxidase (DUOX) genes involved in neutrophil recruitment and inflammation. To determine whether DUOX gene activation plays a role in the severity of PM-induced lung inflammation, DUOX-knockout (KO) and wildtype (WT) mice were exposed to house dust mite (HDM) allergen to produce an allergic mouse model and ambient PM2.5 collected from Sacramento, California. The study was designed to determine if exposure to PM2.5+HDM would cause an exacerbated asthmatic response in either KO or WT mice compared to HDM alone, PM alone or sham controls. S129 mice 12-to-14-weeks of age were administered via intranasal instillation phosphate-buffered saline (PBS), PM2.5, HDM, or HDM+PM2.5 on days 1, 3, and 5 (sensitization period) and PBS or HDM on days 12, 13, and 14 (challenge period). On the 15th day of the experiment, mice were then examined for the degree of allergic response using pulmonary function testing, the degree of lung inflammation by bronchoalveolar lavage, and lung histopathology. The KO mice were found to exhibit less elevated levels of asthmatic-like symptoms when compared to treatment-matched WT mice, suggesting DUOX gene expression plays a critical role in the induction of asthma-like symptoms.