Porcine epidemic diarrhea virus (PEDV) has proven to be a major problem for the porcine industry worldwide. Conventional injectable vaccines induce effective systemic immune responses but are less effective in preventing PEDV at mucosal invasion sites, including the nasal or oral mucosa. Additionally, antigens delivered orally are easily degraded. Nasal immunization induces intestinal mucosal immune responses, which can aid in blocking viral invasion, and requires fewer antigen inoculation doses. Therefore, nasal immunizations are considered to be a potential approach to overcome viral infections. In the present study, nasal immunization of piglets was performed using inactivated PEDV combined with as an immunopotentiator and the efficacy of nasal immunization was assessed. The results demonstrated that compared with oral immunization, piglets from the nasal immunization group exhibited higher levels of neutralizing antibodies (P<0.01) in the intestine, PEDV-specific immunoglobulin (Ig)G (P<0.01) in serum and PEDV-specific secretory IgA (SIgA) in saliva (P<0.01) and nasal secretions (P<0.01). An increased number of intestinal CD3 T cells, IgA-secreting cells and intraepithelial lymphocytes (P<0.05) were also observed. Furthermore, the protein expression levels of interleukin-6 and interferon-γ, relative to the control PEDV infection, were also significantly elevated (P<0.05). The results of the present study indicate that nasal immunization is more effective at inducing the intestinal mucosal immune response, and provide new insights into a novel vaccination strategy that may be used to decrease the incidence of PEDV infections.