Background and aim High density lipoprotein(HDL) has antiatherogenic effects. Short term HDL injection therapy was shown to regress the atherosclerotic lesion in the acute coronary syndrome patients. We tried to investigate the inhibitory effects of reconstituted HDL (rHDL) on restenosis and its mechanism of action using balloon injury rat carotid artery model. Methods and Results rHDL was prepared with plasma-extracted apoA-I and soybean phosphorylcholine(PC) by a molar ratio of 1 to 150. The right carotid artery of 6 week- old male Sprague-Dawley (SD) rats (n=10) was exposed, inserted with a 2F Fogarty catheter in an isolated arterial segment, and then the endothelium was denuded by moving the catheter back and forth 3-4 times. rHDL (40, 80mg/kg) administration was started 4 hrs before surgery and continued for two consecutive days after carotid injury, once daily Two weeks later, rats were sacrificed and injured carotid arteries were stained with H&E to assess neointima formation. Intima to media ratios was 20-fold and 25-fold lower in 40 mg/kg (p=0.4) and 80 mg/kg rHDL treated group (p<0.006) than in control rats, respectively. While rHDL significantly reduced both PCNA and Ki-67 signal in neointima area, andit induced those signals, especially PCNA, in endothelial cells. in vitro proliferation assays revealed that rHDL induced endothelial cell growth but not smooth muscle cell growth. In addition, infiltration of inflammatory cells, such as monocytes and neutrophils, matrix metalloproteinases(MMPs) production and elastin degradation are dramatically reduced by rHDL administration. Inflammatory cells in the lesions might have originated from adventitial side rather than from denuded endothelial side of blood vessel. These inhibitory functions are initiated as early as at day 4 in which administered rHDL intensely resides in the lesion. Expression of HSP27 was decreased in deep intima of injury group whereas the expression level of HSP27 in those of rHDL treated groups was similar to that of uninjured group. HSP27 in smooth muscle cells is time-dependently induced by rHDL or ApoAI. Conclusions: rHDL effectively lowered restenosis by reducing monocytes/neutrophils infiltration, and smooth muscle cell proliferation, MMPs production and elastin degradation, which are also major factors affecting the progression of restenosis and atherosclerosis. In conclusion, HSP27 may play important roles in ameliorating the development of restenosis.