Previous investigations demonstrated that the envelope glycoprotein E2 (gp55) of classical swine fever virus (CSFV) is the most immunogenic protein. Interestingly, recombinant protein E2 that contains only one structural antigenic unit (unit B/C or A) could protect pigs from a lethal challenge of CSFV. Based on these findings, we designed and prepared five overlapping synthetic peptides that covered the sequence unit B/C (aa 693-777) of Shimen E2 and conjugated individual peptides with bovine serum albumin (BSA). After the vaccination, the specificity of the rabbit sera was analyzed in the enzyme-linked immunosorbent assay (ELISA) and the fast protein liquid chromatography (FPLC). The results show that each of the five candidate peptide-vaccines can successfully induce a high titer of specific antibodies in New Zealand White Rabbits (n=3). Subsequently, the five candidate peptide-vaccines were applied in combination for immunization of pigs (n=10) and induced specific and strong humoral responses against all of the five designed peptides in pigs. Our studies indicate that the candidate multi-peptide-vaccine would prove an excellent marker vaccine against CSFV and provide a model for developing effective synthetic peptide vaccines to stop viral epidemics in humans and animals.