Objective To study the effect of a Chinese medicine, Huanglian Jiedu Decoction (HLJDD), on atherosclerotic plaque, inflammatory factors and regulatory T cells in ApoE^-/- mice. Methods High fat diet was given to ApoE^-/- mice to establish an atherosclerosis model. 40 male ApoE^-/- mice were randomly divided into five groups:model group, simvastatin group, low, moderate and high dose HLJDD groups (n=8). HLJDD was intragastrically administered in a dose of 3.5, 7.0, or 14.0 g/(kg·bw) once dailg for 16 weeks. The dose of simvastatin was 5.0 g/(kg·bw). Another 8 male C57BL/6J mice were taken as control group. At the end of the 29-week experiment, all of the mice were sacrificed. The aortic plaques, level of blood lipids, inflammatory factors, Tregs number and the level of Foxp3 mRNA were detected and analyzed by ELISA, flow cytometry and RT-PCR, respectively. Results Compared with the control group, the aortic plaques were much larger in the model group, and the levels of TC, TG, LDL-C, IL-6, hs-CRP, and TNF-α were significantly higher than those in the control group (P < 0.01 for all). Meanwhile, the levels of HDL-C, IL-10, TGF-β and Foxp3 mRNA were much lower than those in the control group (P < 0.01 for all), and the Tregs numbers were less than that in the control group (P < 0.01). HLJDD regulated the blood lipids in ApoE^-/- mice and decreased the levels of IL-6, hs-CRP, andTNF-α, however increased the levels of IL-10, TGF-β and Foxp3 mRNA. At the same time, it increased Tregs number in the ApoE^-/- mice. Compared with the model group, the difference was statistically significancet (P < 0.01). Conclusions HLJDD can significantly alleviate the aortic plaque damages in ApoE^-/- mice.It may be related to the up-regulation of Tregs, which can lead to decrease the expression of serum pro-inflammatory factors such like IL-10, hs-CRP and TNF-α.