Nanoparticle delivery systems have been widely investigated as new vaccines strategy to enhance the immune responses to antigens against infectious diseases. The positively charged nanoparticles could efficiently improve the immune responses due to targeting and activating the antigen-presenting cells. In this study, the immunopotentiator Angelica sinensis polysaccharide (ASP) was encapsulated into Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and the polyethylenimine, one of the cationic polymers, was used to coat nanoparticles to develop a new nanoparticle delivery system (ASP-PLGA-PEI) with positively charged. The ASP-PLGA-PEI nanoparticles significantly activated macrophages, and promoted the expression of the MHCII and CD86 and the production of IL-1β and IL-12p70 cytokines of macrophages. Furthermore, the antigen adsorbed on the surface of the ASP-PLGA-PEI nanoparticles enhanced the antigen uptake by macrophages. Moreover, the mice immunized with PCV2 antigen adsorbed ASP-PLGA-PEI nanoparticles significantly enhanced PCV2-specific IgG immune response and the levels of cytokines, induced a mixed Th1/Th2 immune response with Th1 bias compared with other groups. These findings demonstrate that the positively charged nanoparticles (ASP-PLGA-PEI) have the potential to serve as an effective vaccine delivery and adjuvant system to induce vigorous and long-term immune responses.