In order to explore the safe and effective adjuvant for promotion of immunity of animals against infection, the experiment was carried out to shuffle Tibet pig IL-2 cDNAwith other IL-2 cDNAfrom human, yak and mouse, and the effect of shuffled IL-2 (IL-2S) gene in vivowas investigated on immunity of mice to Pasteurella multocida. The IL-2S protein was found to remarkably promote the proliferation of pig lymphoblasts than the native pig IL-2 protein. Then the IL-2S gene was cloned into VR1020 eukaryotic plasmid (VRIL2S) and enwrapped with chitosan nanoparticles (CNP-VRIL2S). Twenty-one day old female Kunming mice were muscularly inoculated respectively with the CNP-VRIL2, CNP-VRIL2S and CNP-VR1020 along with Pasteurella multocida vaccine, and orally challenged with virulent Pasteurella multocida on 28 days post-vaccination. The blood was weekly collected to detect the change of IgG, IgA, IgM, specific antibody, IL-2, IL-4 and IL-6 by ELISA. The immunoglobulins, specific antibody and interleukins significantly increased in CNP-VRIL2S group compared with the control mice after vaccination and challenge, and 9 of 10 immunized mice survived challenge, while the all control mice manifested severe symptoms and lesions, and finally died of infection. These indicated that VRIL2S entrapped with CNP is a novel safe and effective adjuvant to boost the specific immunity and resistance of animal against infectious pathogen, which could facilitate the development of highly promising powerful adjuvant.