Abstract: six to eight-week-old BALB/c mice and guinea pigs were immunized with eukaryotic plasmids and normal FMDV type O vaccine by intramuscular injection, respectively for three times, and immunization interval was two weeks. The F fragment codes for the amino acids at sites 140-160 and 200-213, the major antigenic epitopes of FMDV type O. The immune effects of DNA vaccines were compared with that of conventional vaccine at MTT, T lymphcyte subgroup, neutralizing antibody, resistance to FMDV and histopathology. The results showed that DNA vaccines pcDNA-VPI and pcDNA-F could induce humoral and cellular immunity. BALB/c mice and guinea pigs immuned with pcDNA-F could were resistant to FMDV, but there were difference with conventional vaccine.