Aim The aim of this study was to examine the effect of naturally regulatory T cells on atherosclerosis plaque in apoliprotein(apo)E~(-/-) Mice,through negative regulating FOXP3 gene. Methods Lentivirus-mediated(siRNA) was used and Foxp3high+⁺ CD25+ Treg cells adoptive transfer assays in high fat diet ApoE~(-/-) Mice were done.Its number was identified by FACS.Inflammatory cytokines were determined by ELISA and the area of atherosclerosis plaque was analyzed. Result We found that the number and function of Foxp3+⁺CD25+ Treg cells in mice injected with Foxp3high+⁺ CD25+ Treg cells was significantly high compared with those of mice injected with FOXP3-siRNA lentivirus. Conclusion Naturally regulatory T cells regulated negatively can promote significantly the progression of atherosclerosis plaque in ApoE~(-/-) Mice.