The typical clinical symptoms of allergic rhinitis (AR) are known to be associated with allergen exposure; however, the underlying mechanisms are not fully understood. We wanted to gain a comprehensive view of the molecular mechanisms related to allergen exposure in a well-controlled mouse model of AR.An OVA-induced AR model was developed. Two hours and 4 weeks after the last OVA challenge, AR symptoms and local immune responses were assessed. At the same time, differentially expressed genes (DEG) in nasal mucosa were identified by gene expression microarray and further analyzed by bioinformatics methods. Verification of DEG was done by quantitative RT-PCR and immunohistochemistry.The number of nasal rubbings and sneezes, serum OVA-specific IgE concentrations, and the number of neutrophils and eosinophils in the nasal mucosa were significantly increased at 2 h and decreased at 4 weeks after the last allergen challenge compared to controls. A total of 2119 DEG were identified, and their expression dynamics were clustered into 8 profiles. Enriched functions in Profile 5, which had a similar trend to clinical features, were mainly related to inflammatory and immune response to environmental factors, eosinophils and neutrophils chemotaxis, and cell migration. Gene co-expression Network for genes from profile 5 identified BCL3, NFKB2, SOCS3, and CD53 having a higher degree. Profile 6 showed persistence of inflammatory and immune response at 4 weeks after the last allergen challenge. Olfactory and coagulation functions were enriched mainly in profiles with downward trends.A wide range of genes with sequential cooperative action were identified to be associated with allergen exposure in AR. BCL3 may be the most vital in symptoms manifestation. Moreover, some inflammatory responses persisted for a period after allergen exposure, supporting a new treatment strategy of targeting inflammation out of season. This study may contribute to a better understanding of AR pathogenesis and provide potential therapeutic targets for AR patients.© 2022. The Author(s).