Background: Unmethylated CpG can induce Th1 and regulatory T cell immune responses and may modulate ovalbumin-induced mouse allergic asthma. However, the effects of CpG in a cockroach allergen asthma model have not yet been elucidated. Objective: To evaluate whether unmethylated CpG can prevent the development of indoor allergen-induced allergic asthma. Methods: Effects of CpG were evaluated using a cockroach allergen-induced mouse model. CpG and Blattella germanica (CR) allergen were co-administered intranasally, and methacholine airway hyperresponsiveness (MCh-AHR), inflammatory cells and cytokine profiles in BAL fluid and lung histology were evaluated. Result: Co-administration of CpG with CR allergen can prevent the development of MCh-AHR and allergic inflammation in a CR-induced asthma mouse model. Eosinophils, lymphocytes, macrophages and neutrophils in BAL fluid were decreased by the co-administration of unmethylated CpG in an OVA-induced asthma model. The expression of IL-5, IL-13 and IFN-γ in BAL fluid was attenuated by the CpG. Peribronchial, perivascular inflammation, and goblet cell hyperplasia in respiratory epithelium were also markedly attenuated by the CpG. Conclusion: These findings suggest that unmethylated CpG may have role in the immune modulation of allergic asthma induced by indoor allergens