Background Aortic stenosis is the most common valvular heart disease in the western world. An effective strategy to prevent from mild to moderate AS to severe AS should yield major health benefit. Calcium accumulation in the aortic valve is a hallmark of aortic sclerosis and aortic stenosis. We hypothesized an association between ethylenediamine tetraacetic acid(EDTA) and/or statin use and halted the progression of aortic valve calcification occurs secondary to experimental hypercholesterolemia. The purpose of this present study was to examine the preventive effects of chelation liquid(EDTA) in experimental calcific aortic sclerosis. Methods and Results To test this hypothesis, twenty New Zealand White rabbits were fed 1% cholesterol-supplemented diet for 30days. Group 1(n=5), 1%(wt/wt) cholesterol diet; Group 2(n=5), 1% (wt/wt) cholesterol diet plus EDTA(100mg/kg per day); Group 3(n=5), 1%(wt/wt) cholesterol diet plus EDTA and simvastatin(3mg/kg per day); Group 4(n=5), 1%(wt/wt) cholesterol diet plus simvastatin. Our data demonstrated that EDTA reduced the bone matrix protein expression for osteopontin, chondrocyte-like cells and chondrocyte protein(type II collagen) at aortic valve compared with control group. And which lesions have significantly reduced by adding simvastatin. Conclusions Increased macrophage, enchondral bone formation in the aortic valve by experimental hypercholesterolemia were inhibited by EDTA plus simvastatin. Further understanding of processes governing calcific aortic valve may yield new therapeutic option.