Abstract: The objective of this work was to evaluate the adjuvant effects of recombinant plasmid inserted CpG motif ( CpG DNA ) to antigen of type O FMDV(Foot and mouth disease virus) in vivo. Using CpG DNA as an adjuvant coadministrated with commercial killed vaccine or purified antigen of type O FMDV to mice or pigs, the results showed that CpG DNA posses an augmented immune response with significant levels of the specific antibody to antigen after intramuscular immunization in mice, antibody titer was 2fold higher than that of the control vaccine of plasmid vector. In target animal trial, vaccine with CpG DNA covaccinated to pigs also induced over 4 folds antibody titer than that of commercial vaccine alone. Purified antigen vaccine of type O FMDV with CpG DNA, showed potent immunity protective effect, which PD50 value arrives above 1300, was far higher than that of purified antigen vaccine without CpG DNA (only 469). In dosage experiment of recombinant plasmid, vaccine with low dose (50 μg and 200 μg) of CpG DNA initiated significantly increased antibody titer of 1∶1 500, which was 4 to 5fold than that of standard vaccine, while dose of 500 μg was only 2fold. These works proved that the recombinant plasmids of CpG DNA can enhance the level of immune responses to antigen of type O FMDV in swine, and could develop as an ideal adjuvant for practical application.