Allergic rhinitis (AR) is a common disease that requires more convenient, safe and effective antigen‑specific immunotherapies. The present study aimed to investigate the therapeutic effect of intranasal administration of a eukaryotic expression vector co‑expressing Der p2 and A20 protein (pVAX1‑Der p2‑A20) on mice with allergic rhinitis. The pVAX1‑Der p2‑A20 vaccine was prepared and encapsulated into poly(L‑lactide‑co‑glycolide) (PLGA) nanoparticles. An allergic rhinitis Balb/c mouse model was established through intraperitoneal sensitization with recombinant Der p2 and cholera toxin followed by intranasal challenge with recombinant Der p2. The treatment effect of the DNA vaccine on nasal allergic inflammation was evaluated, and serum IgE, sIgE, IgG and cytokine levels were determined by ELISA. The percentage of CD4+CD25+Foxp3+Tregs in the spleen was detected by flow cytometry. The DNA vaccine co‑expressing Der p2 and A20 was successfully constructed and encapsulated into PLGA nanoparticles. Der p2‑A20 DNA vaccine intranasal administration markedly ameliorated Der p2‑induced nasal allergic inflammation. The serum Der p2‑specific IgE, IL‑4 and IL‑13 expression levels were inhibited, while the Der p2‑specific IgG1, IgG2a and IFN‑γ expression levels in the serum and splenic CD4+CD25+Foxp3+Treg population were significantly increased after Der p2‑A20 DNA vaccine treatment. These results indicated that the Der p2‑A20 DNA vaccine alleviates nasal allergic inflammation and promotes splenic Treg population in mice with allergic rhinitis.