BACKGROUND: The murine polyp model was developed previously using ovalbumin and Staphylococcus aureus enterotoxin B (SEB). Here, we established a model mimicking key aspects of chronic eosinophilic rhinosinusitis with nasal polyps using the house dust mite (HDM), a clinically relevant aeroallergen, co-administered with SEB. We assessed the inflammatory response and formation of nasal polypoid lesions in an experimental murine model using intranasal delivery of HDM and ovalbumin. METHODS: After induction of HDM-induced allergic rhinosinusitis in C57BL/6 mice, SEB (10ng) was instilled into the nasal cavity of mice for eight weeks. Phosphate-buffered saline-challenged mice served as control. Histopathological changes were evaluated using haematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and periodic acid-Schiff stain for goblet cells. The distribution of mast cells in mouse nasal tissue was determined by immunohistochemistry. Serum total IgE was measured using enzyme-linked immunosorbent assay. RESULTS: Compared to mice treated with HDM only, the HDM+SEB-treated mice demonstrated nasal polypoid lesion formation and a significant increase in the number of secretory cells and eosinophilic infiltration. Moreover, mice challenged intranasally with HDM showed highly abundant mast cells in the nasal mucosa. In contrast, OVA+SEB-challenged mice showed a significantly lower degree of mast cell infiltration. CONCLUSION: We established an in vivo model of chronic allergic rhinosinusitis with nasal polypoid lesions using HDM aeroallergen. This study demonstrated that the HDM+SEB-induced murine polyp model could be utilised as a suitable model for nasal polyps, especially with both eosinophil and mast cell infiltration.