Background: It is widely accepted that T helper 2 (Th2) cells, Th17 cells and their cytokines orchestrate the feature of asthma. However, most of studies on asthma mechanisms use a single allergen challenge model. Actually, humans are concurrently exposed to various allergens, and the mechanism of asthma with complex allergen exposure is less well defined. To explore whether the mechanism would be altered if asthma patients are re-exposed to another allergen, we exposed the chicken egg albumin (OVA) induced-asthmatic mice to house dust mite (HDM). Methods: HE staining was used to analyze pathologic variation in lung tissue of mice in each sub-group: control group, HDM alone group, OVA alone group and OVA+HDM group. Th1, Th2 and Th17 associated gene mRNA expressions were detected by quantitative PCR; associated cytokines were determined by ELISA or immunohistochemistry. Results: The severe of inflammatory cell infiltration, the augmentation of Th17 and Th2 related gene mRNA expressions and the increase of Th17 associated cytokines expression were shown in OVA+HDM group in comparison with OVA alone group. However, Th2 related cytokines were increased with no significant difference in OVA+HDM group compared with OVA alone group. Conclusions: We have found that Th17 response is connected with inflammation in the OVA-induced asthmatic mice exposed to HDM. When OVA-induced asthmatic mice are re-exposed to HDM, the pathomechanism is different from OVA alone exposure. HDM, indoor allergen, may be an important interferential factor for asthma therapy. It will give an important direction in the development of future asthma therapy