Three candidate cytokines: recombinant porcine interleukin-2 (rpIL-2), rpIL-6 and the fusion protein rpIL6-IL2 were used as adjuvants in this study to investigate the enhanced immune responses to PRV inactivated vaccine (IAV) in pigs. In this natural host trial, we demonstrated that rpIL-2 showed potential adjuvant effects on PRV IAV, which was characterized not only in antigen-specific immune responses, but also in protection against PRV infection. The use of rpIL-2 resulted in significantly higher virus neutralizing (VN) antibody levels and CTL activities on PRV IAV vaccination. The increased PRV-specific secretion of pIL-4 and pIFN-gamma from PBMC of pigs also demonstrated the adjuvant effects of rpIL-2. In addition, the co-administration of the rpIL-2 also produced an improved protection to the viral challenge, demonstrated by significant reduction of the ratios of fever and viral excretion in nasal swabs. However, there was no additional effect of adjuvant induced enhancement of immune responses and protection against challenge with the use of rpIL-6 and rpIL6-IL2 in this study.