Abstract: In order to achieve efficient assembled and expression of virus like particles（VLPs） from different animal epidemics in the same recombinant Escherichia coli, in this study, the nucleotide sequences encoding Porcine circovirus type 2（PCV2） Cap protein and Infectious bursal disease virus（IBDV） VP2 protein were codon-optimized and cloned into pET28 a-Rcodon vector before transformed into BL21（DE3） △lpxM tig⁺ host strain, respectively. The intracellular assemblies of the target proteins were analyzed by nano particle size analyzer and transmission electron microscope, and the vaccines prepared by the purified antigens were used to evaluate the efficacy of immunizing animals. The results showed that the soluble expression level of PCV2 Cap and IBDV VP2 proteins were increased about 90% compared with the control group before optimization respectively, and the target proteins were efficiently self-assembled into VLPs intracellularly and arranged in a uniform lattice structure. The subunit vaccine containing VP2 antigen could provide 100% protective effect. The antibody level of subanit vaccine containing PCV2 antigen was higher than that of negative control group. These results indicated that both PCV2 Cap protein and IBDV VP2 protein were highly soluble expressed and self-assembled into VLPs intracellularly in recombinant Escherichia coli with good immunogenicity, and it could provide better immune protection for immunized animals.