A few members of coronavirus group I which includes porcine epidemic diarrhea virus (PEDV) use porcine aminopeptidase N (pAPN) as a cellular receptor. Cellular receptors play an important role in virus attachment and entry. However, the low permissiveness of PEDV to APN-expressing porcine cell lines has made it difficult to elucidate the role of pAPN in vitro. The purpose of this study was to prove whether the treatment of soluble pAPN could enhance the antibody production against PEDV in guinea pigs, rabbits and sows. The animals (20 guinea pigs, 8 rabbits and 20 sows) were divided into 4 groups. Group A was injected intramuscularly (IM) with soluble pAPN at one hour before intramuscular infection of PEDV on the same site, group B for IM simultaneous injection of pAPN and PEDV, and group C for IM injection of PEDV only. Group D served as a control of pAPN treatment or PEDV infection. Antibody production against PEDV was compared among groups at regular intervals. The results suggested that pAPN could enhance the antibody production against PEDV in guinea pigs and rabbits which are free of pAPN, however, the effect of pAPN treatment in sows was not clearly elucidated.