Objective To establish a rat model of atherosclerosis combined with syndrome of intermingled phlegm and blood stasis, to observe the inflammatory reactions and the treatment effect of prescription (Danlou tablet) on the rat model. Methods Thirty-two healthy male SD rats were randomly and equally divided into four groups, namely, normal control group, model control group, atorvastatin group (ATV group), and Danlou group (DLP group). The normal control group was given basic forage, while other three groups were given high fat forage plus intraperitoneal injection of vitamin D3 and balloon injury of the left common carotid artery to build rat atherosclerosis model combined with syndrome of intermingled phlegm and blood stasis, and then received intragastric administration of saline, atorvastatin suspension and Danlou tablets suspension for 4 weeks, respectively. After intervention, both serum lipid and hs-CRP, IL-6, TNF-α, and LP-PLA2 levels were determined by ELISA, pathological alterations in the thoracic aorta was analyzed using HE staining, the expressions of IL-6, TNF-α and LP-PLA2 mRNA in the thoracic aorta tissue were assessed by real-time fluorescent quantitative PCR technology. Results ① Compared with the normal control group, there were significant increases in serum TC, LDL-C, hs-CRP, IL-6, TNF-α, and LP-PLA2 levels (P<0.05 for all) and decrease of serum HDL-C levels in the model group (P<0.05). The expressions of IL-6, TNF-α, and LP-PLA2 mRNA in the rat aorta were significantly increased (P<0.05 for all). In the model control group, HE staining showed altered arrangement of aortic endothelial cells, irregular intimal thickening, broadened subendothelial space, and accumulation of foam cells and lipid deposition, forming typical atherosclerotic plaques. ② Compared with the model control group, the ATV and DLP groups showed significantly decreased serum TC, LDL-C, hs-CRP, IL-6, TNF-α, and LP-PLA2 levels (P<0.05 for all) as well as the expressions of IL-6, TNF-α, and LP-PLA2 mRNA in the thoracic aorta (P<0.05 for all). There were no significant differences between the ATV and DLP groups (P>0.05). There were also reduced aortic intimal hyperplasia, macrophage infiltration and plaque area compared with those of the model group. Conclusions Rat model of atherosclerosis combined with syndrome of intermingled phlegm and blood stasis can be established by high fat diet feeding combined with the intraperitoneal injection of vitamin D3 and balloon injury of carotid artery. The prescription (Danlou tablet) can inhibit the inflammatory reaction and ameliorate atherosclerotic changes in the rat models.