We herein examined the importance of H2-Eb1 and H2-Ab1 in the susceptibility of mice to allergic rhinitis (AR) by developing double-gene (H2-Eb1+H2-Ab1) knockout mice. The mice were randomly grouped into different sensitization and excitation treatments, then their behavioral scores; nasal mucosa HE staining; thymus tissue toluidine blue staining; levels of ovalbumin (OVA)-specific IgE, IL-2 and IL-13 in the serum; and expression of IL-2 and IL-13 in the nasal mucosa were observed. H2-Ab1 and H2-Eb1 were both successfully knocked out in the study group (KO-OVA). Compared with the control group (WT-OVA), the nasal mucosal tissue in the KO-OVA mice showed fewer histological changes, reduced numbers of eosinophilic granulocytes, fewer mast cells in the thymus tissue, reduced concentrations of OVA-specific IgE and IL-13 in the serum, and reduced expression of IL-13 in the nasal mucosa. The behavior of the mice was also improved. In addition, the IL-2 concentration in the serum and IL-2 expression in the nasal mucosa were increased. There were two important findings of this study: (1) The H2-Ab1 and H2-Eb1 double knockout model of allergic rhinitis was successfully constructed, and the Th1/Th2 cell factors were in imbalance in these mice compared to WT mice; (2) the AR susceptibility of the dual knockout mice was reduced, confirming that H2-Ab1 and H2-Eb1 contribute to allergic rhinitis, at least in mice.