Aim The effects of in vivo administration of human high density lipoprotein (HDL) injection on the development of aortic streaks were studied in cholesterol-fed rabbits. Methods The rabbits received a 1% cholesterol-rich diet for 8 weeks. During this period, the HDL group was intravenously administered with 50 mg/week of HDL injection; the lovastatin group was administered with 10 mg/day of lovastatin via subcutaneous injection; the placebo group received normal saline (0.9% NaCl). The HDL injection was manufactured and provided by Tsinghua Unisplendour Guhan Bio-pharmaceutical Corporation Ltd. During the study, plasma lipid levels followed a similar profile in all groups to cholesterol-rich diet. Results At the completion of study, atherosclerotic-like lipid-rich lesions covered 32.6%±21.7% (x±s), of the intima aortic surface in the placebo group, 9.1%±7.8% in the HDL group, and 20.8%±13.1% in the lovastatin group. The levels of plasma total cholesterol were 10.05±2.30, 2.93±1.41, and 3.74±1.73 g/L in placebo, HDL, and lovastatin groups, respectively. The levels of plasma high density lipoprotein cholesterol (HDLC)were 0.43±0.12, 0.62±0.23, 0.23±0.14 g/L in placebo, HDL, and lovastatin groups, respectively. The value of total cholesterol deposited within vessel wall were significantly lower in the aortas of the HDL group than those in the placebo group and lovastatin group. Human HDL injection showed a more efficient inhibition of atherosclerotic lesions than lovastatin did. Conclusion The administration of human HDL injection to cholesterol-fed rabbits dramatically inhibits the extent of aortic fatty streaks, modifies plasma lipid, and lipid deposition in the arterial wall.