Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causing acute diarrhea, dehydration, and up to 100 % mortality in neonatal suckling piglets, leading to huge economic losses in the global swine industry. Vaccination remains the most promising and effective way to prevent and control PEDV. In this study, we produced PEDV virus-like particles (VLPs) composed of S, M, and E proteins with a baculovirus expression system and a mammalian expression system. The S, M, and E proteins were effectively expressed and successfully assembled into VLPs. Subsequently, S subunits and commercially inactivated vaccines were selected and compared with two VLPs vaccines for immune efficacy through mouse immunization. The results showed that both VLPs induced higher levels of IgG, IgA, and neutralizing antibody titers, lymphocyte proliferation indexes and T, B cell ratios. Compared with the baculovirus VLPs, the mammalian VLPs exhibited better effects in inducing neutralizing antibodies, lymphocyte proliferations, and IFN-γ. These data indicated that the PEDV VLPs vaccine constructed using the mammalian expression system has better immune efficacy and has the potential to serve as a novel PEDV vaccine.