Background: High density lipoprotein(HDL) has been tried to develop as a treatment for the prevention of progression and to induce regression of atherosclerosis. Objective: We tried to prove the antiatherosclerotic effects of reconstituted HDL(rHDL) in the apo E-/- mice. Methods and materials: rHDL consists of apolipoprotein A-I isolated from human plasma and phosphatidylcholine from soybean in a weight ratio 1:4. Apo E-/- mice (n=7) were fed high fat high cholesterol diet(HFHC) from 8 weeks to 20 week of age. After 8weeks of HFHC diet 150 g of rHDL was administered through tail vein, twice weekly for 4 weeks. Reference apoE-/- mice (n=7) were fed HFHC diet for 12 weeks. At 20 week of age, mice were euthanized and atherosclerotic lesions were examined with oil red o staining. Macrophage staining was done using CD68 Ab and smooth muscle staining was done using –smooth muscle cell actin, HSP27, MMP9 and apolipoprotein B levels were measured by confocal microscope. Results: Oil red O positive stained areas in aorta were 30.8% decreased in the mice injected with rHDL(reference, 0.405  0.045 mm2 vs rHDL, 0.279  0.0908 mm2 p <0.01). Macrophage infiltrating areas in the cross section at aortic sinus were 30% decreased in the rHDL treated group (reference, 0.0981  0.0357 mm2 vs rHDL, 0.0593  0.0180 mm2 p<0.025 Confocal microscopic examination revealed that rHDL diminished the MMP9 secretion and apolipoprotein B but up-regulated HSP27 levels in the atherosclerotic lesion. Medial smooth muscle cell areas, collagen III and IV contents were not significantly different between two groups. Also serum lipid profiles (total cholesterol, triglyceride) and liver enzymes(GOT, GTP) were similar between two groups. Conclusion: rHDL treatment significantly decreased the atherosclerotic lesion and macrophage infiltration in the apoE-/- mice fed HFHC diet.