Abstract：Objective：To observe the anti-inflammatory and antioxidative stress effect of Yiqi Huayu Huotan prescription on rats with atherosclerosis (AS). Methods：A total of 24 male Wistar rats were randomly divided into the control group，the model group and the administration group，8 rats in each group. In the model group and the administration group，the rat models were established by high fat diet and intraperitoneal injection of 60 IU/kg vitamin D3 at a dose of 2 mL/kg， for 12 weeks. The administration group was given 100 mg/kg Yiqi Huayu Huotan prescription by gavage per day during the model establishment，and the control group and the model group were given saline of the same volume by gavage. After 12 weeks， the serum of rats was collected for HE staining， and then the morphometric structure of aorta was observed. The ELISA method was applied to detect the contents of and high- density lipoprotein cholesterol(HDL- C)， low- density lipoprotein cholesterol (LDL-C)，total cholesterol (TC)，triglyceride (TG)，C-reactive protein (CRP)，tumor necrosis factor-α (TNF-α)， interleukin- 6 (IL- 6)， superoxide dismutase (SOD)， catalase (CAT)， malondialdehyde(MDA) and reactive oxygen species (ROS) in serum. The protein immunoblotting method was used to detect the expression of nuclear factor κB (NF-κB) in aorta. Results：Compared with those in the control group，in the observation group，there were intimal thickening and damage as well as incomplete arrangement of endothelial cells at the lesion site of aorta；the levels of LDL-C，TC，TG，CRP，TNF-α， IL- 6， NF- κB， MDA and ROS in the observation group were significantly increased(P ＜0.05)， and the levels of HDL- C， SOD and CAT were significantly decreased (P ＜0.05). Compared with those in the model group，in the administration group， the intima was smooth；the levels of LDL-C，TC，TG，CRP，TNF-α，IL-6，NF-κB，MDA and ROS were significantly decreased (P ＜0.05)，and the levels of HDL-C，SOD and CAT were significantly increased (P ＜0.05). Conclusion：Yiqi Huayu Huotan prescription can prevent AS in rats via the inhibition of inflammation and the improvement of oxidative stress.