To develop a CpG containing oligodeoxynucleotide (CpG ODN)-enhanced rabies vaccine for stimulating an earlier production of rabies virus neutralizing antibody (RVNAb) with high titers, we designed a CpG ODN (BW006) and evaluated its adjuvant activities in enhancing the immune response to rabies vaccine with or without aluminum in mice. It was found that BW006 could facilitate the rabies vaccine to induce an earlier and more vigorous RVNAb response, resulting in more effective protection of mice from rabies virus challenge. In addition, three shots of rabies vaccine with BW006 induced compatible RVNAb level with that induced by five shots of aluminum-adjuvanted rabies vaccine. These data reveal that BW006 could be used as a promising adjuvant to replace of or combine with aluminum for developing more effective rabies vaccines.