ObjectiveTo study the intervention of Huanglian Jiedutang on atherosclerosis （AS） in apolipoprotein E knockout （ApoE^-/-） mice induced by the high-fat diet. MethodThe ApoE^-/- mouse model of AS was induced by the high-fat diet， and Huanglian Jiedutang was used to intervene in the AS in the ApoE^-/- mice. The pathological changes of aorta were observed by hematoxylin-eosin （HE） staining. The levels of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected by an automatic biochemical analyzer. The protein expression levels of sirtuin-1 （SIRT1） and nuclear factor-kappa B （NF-κB） were determined by Western blot assay， and the mRNA expression levels of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferators-activated receptors α （PPARα）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and NOD-like receptor pyrin domain-containing 3 （NLRP3） were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， there was a large amount of lipid accumulation in the blood vessels of the model group. In the model group， the levels of serum TG， TC， and LDL-C were increased （P<0.01）， and the level of HDL-C was decreased （P<0.01）. The protein expression level of SIRT1 in the aorta was decreased， while that of NF-κB was increased in the model group （P<0.01）. The mRNA expression levels of IL-6， TNF-α， and IL-1β were higher （P<0.01）， while those of AMPK in the liver were lower in the model group （P<0.01）. Compared with the model group， the Huanglian Jiedutang group reduced the lipid accumulation and inflammatory reaction in the aorta of mice with AS， reduced the levels of TC， TG， and LDL-C （P<0.01）， and increased the level of HDL-C （P<0.01）. Huanglian Jiedutang significantly increased the protein expression level of SIRT1 in the aorta of ApoE^-/- mice （P<0.01） and decreased the protein expression levels of NF-κB in the aorta （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA expression levels of TNF-α， IL-6， IL-1β， and NLRP3 in the aorta （P<0.05， P<0.01）， and up-regulated the mRNA expression levels of AMPK and PPARα in the liver of ApoE^-/- mice （P<0.05， P<0.01）. ConclusionHuanglian Jiedutang has a certain intervention effect on the formation of atherosclerotic aortic plaque in ApoE^-/- mice. Its mechanism may be related to the decrease of serum TC， TG， and LDL-C levels， the increase of HDL-C levels， thus playing a role in lowering blood lipid， the increase of SIRT1 protein， the decrease of NF-κB protein， the decrease of inflammatory factors such as TNF-α and IL-6， which protects blood vessels from inflammatory injury， and the improvement of AMPK and PPARα levels to participate in autophagy and apoptosis.