To explore development of a vaccine against PCV2 infections, the gene of capsid protein (Cap) was inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus expressing capsid protein (rSPV-cap) was verified by PCR, western blot and immunofluorescence assays. To evaluate the immunogenicity of rSPV-cap, twenty-four PCV2 seronegative minipigs were immunized with rSPV-cap, wild type SPV (wtSPV; negative control), or PBS (challenge control). After inoculation with PCV2, pigs in the rSPV-cap immunized group showed significantly higher average daily weight gain (ADG) and shorter fever duration compared with the wtSPV treated group (P<0.05). Cap-specific antibody in the rSPV-cap immunized group increased dramatically after vaccination and increased continuously over time. PCV2 genomic copies in the serum of rSPV-cap immunized pigs were significantly less compared with the wtSPV treated group at all time points after inoculation (P<0.01). Significant reduction in gross lung lesion scores, histopathological lung lesion scores, and lymph node lesion scores were noted in the rSPV-cap immunized group compared with the wtSPV treated group (P<0.01). The results suggested that the recombinant rSPV-cap provided pigs with significant protection from PCV2-associated disease; thus, it offers proof-of-principle for the development of a vaccine for the prevention of PCV2-associated disease in pigs.