Objective To establish and optimize the animal model of atopic march (AM), the skin and lung tissue sensitization under conditions of single or combined modeling of OVA and MC903 were compared. Methods 40 SPF BALB/c mice aged 6~8 weeks were randomly divided into control group, model group A, model group B and model group C. The three AM models were established with MC903, MC903+OVA and OVA, respectively, through twice skin sensitization and once respiratory sensitization. Skin sensitization severity scoring system, immunohistochemistry and enzyme-linked adsorption assay were used to compare skin lesion morphology, skin or lung histopathology and immunophenotype. Results Compared to OVA or MC903 modeling alone, MC903+OVA modeling mice showed more significant changes in skin morphology, higher score of skin sensitization severity, more severe skin and airway inflammatory cell infiltration, and more significant changes in the expression of related inflammatory factors TSLP, IL-4, IL-13 and IL-10 (all P <0.05). Conclusion The AM animal model optimized by MC903 combined with OVA was successfully constructed, which provided a good methodological basis for AM mechanism research.