Aim To observe the effect of Huayu Qutan recipe on regulating the expression of HIF-1α/VEGF/VEGFR-2 pathway on the aortic lipid plaque in As rabbits and to explore the mechanism of the Huayu Qutan recipe on the atherosclerotic plaque. Methods Sixty New Zealand rabbits were randomly divided into the control group (n=15) and the experimental group (n=45). Rabbits in the experimental group were prepared as atherosclerotic rabbit model by immune-induced endothelial injury and by feeding with high-fat diet. The control group was given normal feed. After 8 weeks, the rabbits in the experimental group were randomly divided into the model group, the Huayu Qutan recipe group and the Simvastatin group. Each group was given the corresponding drug intervention; the control group and the model group were given the same volume of saline, one time a day for 4 weeks before taking materials. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol (HDLC) in serum were detected by the automatic biochemical analyzer. HE staining and the oil red O staining were used to observe the pathological changes of the aorta in rabbits. The thickness of the intima and tunica media was measured in aortic wall. Immunohistochemical method was adopted to determine CD31 mean optical density value. The contents of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor(VEGF) in serum were detected by ELISA. Western blot was used to detect the expression of HIF-1α, VEGF and VEGFR-2 in the aorta. Results Compared with the control group, the levels of TG, TC and LDLC in the model group were significantly increased (P<0.01) and HDLC levels were significantly decreased (P<0.01). Compared with the model group, the levels of TG, TC and LDLC in the Huayu Qutan recipe group and the Simvastatin group were significantly decreased (P<0.05 or P<0.01), and HDLC content was significantly increased (P<0.05 or P<0.01). Compared with the control group, the thickness of intima and tunica media were significantly increased in the model group (P<0.01) . Compared with the model group, the thickness of intima and tunica media were significantly decreased in the Huayu Qutan recipe group and the Simvastatin group (P<0.01). Compared with the control group, the CD31 mean optical density value were significantly increased in the model group (P<0.01). Compared with the model group, the CD31 mean optical density value were significantly decreased in the Huayu Qutan recipe group and the Simvastatin group (P<0.01). Pathological staining showed the aortic intimal hyperplasia, a large number of foam cells and lipid deposition in the model group. After the treatment of the Huayu Qutan recipe and the simvastatin, they were significantly improved. Compared with the control group, the contents of HIF-1α and VEGF were significantly increased in the model group (P<0.01). Compared with the model group, the levels of HIF-1α and VEGF were significantly decreased in the Huayu Qutan recipe group and the Simvastatin group (P<0.05 or P<0.01). The expressions of HIF-1α, VEGF and VEGFR-2 in the aorta of the model group were significantly higher than those in the normal group (P<0.01). After treated by the Huatan Qutan recipe and the Simvastatin, the expression of HIF-1α, VEGF and VEGFR-2 in the two groups were significantly lower than those in model group (P<0.01). Conclusion The Huayu Qutan recipe stabilizes the As lipid plaque and the mechanism may be related to the regulation of HIF-1α / VEGF / VEGFR-2 pathway to inhibit angiogenesis.