Porcine circovirus type 2 (PCV2) can cause postweaning, multisystemic wasting syndrome in pigs, which leads to enormous losses in the swine industry worldwide. Here, a genetically engineered Lactococcus strain expressing the main protective antigen of PCV2, the Cap protein, was developed to act against PCV2 infection as an oral vaccine.Expression of the Cap protein was confirmed via western blot, ELISA and fluorescence microscopy. Over 90% of the recombinant pAMJ399-Cap/MG1363 survived a simulated gastrointestinal transit. It also survived the murine intestinal tract for at least 11 days. Then, the safety and immunogenicity of pAMJ399-Cap/MG1363 in orally immunized mice was evaluated. The levels of the sIgA, IgG and cytokines (IL-4 and IFN-γ) obtained from the mice immunized with pAMJ399-Cap/MG1363 were significantly higher than those in the control groups.pAMJ399-Cap/MG1363 can survive in the gastrointestinal transit and effectively induce mucosal, cellular and humoral immune response against PCV2 infection via oral administration.This study demonstrates the potential of the genetically engineered Lactococcus lactis as a candidate for an oral vaccine against PCV2.