Interleukin-2 (IL-2) is vital to elicit and amplify the cellular and humoral immune responses to foreign antigens, which is extensively utilized in the control of infectious disease and treatment of various cancers. Porcine and murine IL-2 genes were, respectively, subcloned into VR1020, designated as VPIL-2 and VMIL-2, and then encapsulated in chitosan nanoparticles (CNP) prepared by ionic linkage. The BALB/c mice were intramuscularly co-administrated with chitosan-IL-2 nanoparticles (CNP-IL2) and paratyphoid vaccine to test the adjuvant effect of CNP-IL2. On day 35, the immunized mice were orally challenged with virulent Salmonella. The content of IgG, IgA, IgM, IL-2, IL-4, IL-6 and specific antibody titer as well as the number of immunocompetent cells were systematically analyzed in the vaccinated mice. The results revealed that the levels of immunoglobulins, cytokines, the specific antibodies, together with the numbers of lymphocytes significantly increased in vaccinated mice inoculated with CNP-VPIL2 in contrast with those with naked IL-2 plasmids and blank plasmids. The CNP-VPIL2 immunized mice exhibited higher humoral and cellular immune responses, less severe clinical signs and lesions of disease caused by the bacteria than the other groups after challenge. These findings suggest that CNP-VPIL2 has a significant enhancement effect on immune responses of mice, which results in better immunoprotection against Salmonella infection, indicating that CNP-VPIL2 could be employed as an effective immunoadjuvant to elevate immunity of animals to conventional vaccines.