The aim of this study was to develop a mouse model of chronic eosinophilic rhinosinusitis. Mice were sensitized to Aspergillis fumigatus (Af) extract by intraperitoneal injection. The animals subsequently received nasal challenges with Af extract 3 times per week for 12 weeks. Sinonasal complexes were studied histologically by the study otolaryngologists and pathologists to characterize the inflammatory response. Animal care facility at an academic institution. A chronic eosinophilic inflammatory response was evoked in all study animals. Statistical analysis was performed for inflammation, secretory cell hyperplasia, mast cells, and eosinophils. There were very significant differences (P < 0.0005) between control and study mice in all categories. Prolonged nasal challenge of Af extract creates an inflammatory response in murine nasal mucosa that mimics human chronic eosinophilic rhinosinusitis. A murine model for chronic rhinosinusitis is reported that may facilitate future investigations into disease pathophysiology. EBM rating: B-2