Aim To study the effect of atorvastatin on the expression of cyclooxygenase-2(COX-2) and other proinflammatory molecules in a rabbit model of atherosclerosis and to further explore the potential mechanism of atorvastatin in anti-atherosclerostic inflammation beyond the lowing lipid. Methods Twenty-four male New Zealand rabbits(3 months old)were fed with normal diet(n=8) and high-cholesterol diet(n=16) respectively for 8 weeks,and then the high-cholesterol diet rabbits were assigned to receive either atorvastatin 2.5 mg/(kg·d)(n=8)or starch(n=8).6 weeks later,aortas were removed under deep anesthetization.The femoral arteries were removed to determine COX-2 mRNA by reverse transcription-polymerase chain reaction and the level of COX-2 and matrix metalloproteinase-9(MMP-9) protein by immunohistochemistry. Atherosclerotic lesions were measured by experienced pathologist under Beihang Pathology Imaging Analysis System in aortas from hypercholesterolemic rabbits.Plasma interleukin-6(IL-6) levels were measured by enzyme linked immunosorbent assay(ELISA). Results Compared with placebo-treated group,atherosclerotic area was reduced in atorvastatin-treated group(43.0%±12.5% vs 83.0%±11.6%,p<0.05).COX-2 mRNA expression in aortas from hypercholesterolemic rabbits were significantly increased compared with those from normal rabbits,and significantly reduced by the treatment of atorvastatin(1.03±0.09 vs 0.57±0.10,p<0.05),and the levels of COX-2 mRNA expression were related to both atherosclerotic area and plasma IL-6 levels(r=0.803 and 0.795,both p<0.05).Expression of COX-2 protein in atherosclerostic plaques were significantly increased and reduced by the treatment of atorvastatin(62.4%±8.5% vs 34.3%±8.8%,p<0.05),and the levels of COX-2 were related to the levels of MMP-9 in atherosclerostic plaques(r=0.815,p<0.05). Conclusion In hypercholesterolemic rabbits,atorvastatin can decrease circulating IL-6 level and MMP-9 level in plaque,and the potential mechanism of atorvastatin in anti-atherosclerostic inflammation may be through the COX2 signal pathway.