Objective To compare the differences in airway immune inflammation between two sensitizationpathway-induced allergic airway inflammation mouse models and to provide a reference for the study of allergic asthma murine models. Methods Murine models of allergic airway inflammation were established by intraperitoneal or epicutaneous sensitization with ovalbumin. Total IgE and OVA-specific IgE levels in mouse serum were analyzed by ELISA. Bronchoalveolar lavage fluid cells were stained with Wright-Giemsa stain to assess eosinophilic airway inflammation. Hematoxylin and eosin and periodic acid-Schiff staining were performed on lung tissue to assess histopathological changes, and lung immune cells were subjected to mRNA sequencing and data analysis. Results Both intraperitoneal and epicutaneous sensitization-induced allergic airway inflammation mouse models exhibited inflammatory responses, with eosinophil infiltration of lung tissue, bronchial epithelial club cell hyperplasia, and upregulation of Th2-Type cytokine expression. However, systemic immunity was stronger in the intraperitoneal sensitization model, and local immunity was stronger in the epicutaneous sensitization model. Asthma-related pathways, such as the JAK-STAT signaling pathway, were upregulated in both models, whereas the Hippo pathway was downregulated only in the epicutaneous sensitization model. The epicutaneous sensitization model was more closely associated with the increase of metalloproteinases, mast cells, and basophils. Conclusions The different pathways of allergen intraperitoneal and epicutaneous sensitization induce different immunological phenotypes and molecular mechanisms of airway inflammation in mouse models of allergic airway inflammation.