Aim To evaluate the effect of recombinant human vascular endothelial growth factor 165(VEGF165) on progression of atherosclerotic plaque in rabbits. Methods Fifteen rabbits were randomly fed with normal diet or high cholesterol diet. Albumin or VEGF165 was administered by a single-intramuscular injection(2 μg/kg)to rabbits fed with cholesterol diet begining three weeks before therapy. Subsets of rabbits from control group, high cholesterol group and VEGF group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analysis at 42 days. Results In control group, high cholesterol group and VEGF group, significant difference was shown in comparing mean plaque area (0% vs. 1.81%±0.61% vs. 24.12%±3.58%), plaque circumference (0% vs. 6.05%±1.62% vs. 25.71%±1.97%) and maximal plaque thickness (0 vs. 0.06 mm±0.002 mm vs. 0.16 mm±0.007 mm)respectively. There were significant differences(p<0.05) in neovascularization density (number of CD34-positive cell, 0 vs. 12.35±2.02 vs. 61.15±7.55 cells/ mm 2 ) in control group, high cholesterol group and VEGF group at 42 days. Transmission electron microscopy showed intimal vessels were associated with lesion and the capillary lumen contain lymphocytes. There was positive correlation between CD34 positive area and plaque area (r=0.989, p<0.001)in VEGF group. Conclusions Vascular endothelial growth factor 165 increased the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.