Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection.