To explore the effects of Modified Ling-Gui-Zhu-Gan Decoction combined with calorie restriction on atherosclerosis of apoE-/- mice.Methods:C57BL/6 mice fed with general fodder were selected as the normal control group(Group A); apoE-/- mice fed with high-fat diet were randomly divided into the model group(Group B)，Modified Ling-Gui-Zhu-Gan Decoction(LGZG) group(Group C)，calorie restriction group(Group D) and Modified Ling-Gui-Zhu-Gan Decoction combined with calorie restriction group(Group E).Of these groups，Groups B and C were fed with high-fat diet，Groups D and E were fed with 50% calorie restricted high-fat diet as compared with mice in Group B，Groups C and E were administrated with 2 mL LGZG decoction by gavage，and other groups were given the same amount of normal saline by gavage.After 12 weeks，blood was collected and the thoracic aorta was retained，plasma lipid and inflammatory cytokine levels were detected by enzyme linked immunosorbent assay(ELISA)，atherosclerotic plaque in the lumen was observed by hematoxylin-eosin(HE) staining，and AMPK，p-AMPK，PPARα，NF-κB and p-NF-κB protein expressions in the plasma lipid，inflammatory cytokine and aorta were measured by Western Blotting.Results:Compared with Group B，Groups C，D and E demonstrated more alleviative atherosclerotic lesions with obvious decrease of the ratio of plaque area to luminal area(P<0.05 or P<0.01); serum TC，TG，LDL-c，TNF-α，IL-6 and IL-1β concentrations were significantly lower than those in Group B(P<0.05 or P<0.01); minimal atherosclerotic lesions were observed with the minimal ratio of plaque area to luminal area in Group E The results of Western Blot showed that the protein levels of p-AMPK and PPARα in Group E significantly increased(P<0.01)，while those of p-NF-κB was significantly reduced(P<0.01).Conclusion:LGZG Decoction combined with calorie restriction has anti-atherosclerotic effects，whose mechanism may be that the AMPK/PPARα signaling pathway is activated by reducing the plasma lipid and inflammatory reaction，thereby inhibiting the activity of NF-κB and effectively playing the anti-atherosclerotic effects.