Hypercholesterolemia is a form of high blood cholesterol that leads to the condition of atherosclerosis, causing stroke and coronary heart disease. Chromolaena odorata L. leaves is one of the medicinal plants that can be used as an alternative antihypercholesterolemic, because it contains alkaloids, flavonoids, tannin saponins and steroids. This study aims to determine the antihypercholesterolemic activity and the best dose of ethanol extract of Chromolaena odorata L. leaves, on male Rattus norvegicus L. induced by high fat diet. A total of 25 male rats were divided into 5 groups. All groups were adapted for 7 days and their total cholesterol levels (T0) was measured. In the next 10 days, the rats were conditioned to hypercholesterolemic by giving 10 ml/kg BW of quail yolk. The total cholesterol levels then measured (T10). After that, al the 5 groups received a different treatment for 14 days, group I was given 0,18 mg/200 gr BW of simvastatin, group II was given 0,5% of sodium CMC, group III, IV and V were given the ethanol extract of Chromolaena odorata L. leaves respectively 20 mg/kg BW, 40 mg/kg BW and 60 mg/kg BW and the total cholesterol levels were measured (T24). The method used to measure the total cholesterol levels is CHOD-PAP. The data obtained were analyzed with Kruskal-wallis and Mann whitney test. The statistic result showed an antihypercholesterolemic activity of the three doses of ethanol extract of Chromolaena odorata L. leaves. The best dose in reducing the total cholesterol levels compared to simvastatin is 60 mg/kg BW. Keywords: Antihypercholesterolemic, ethanol extract of Chromolaena odorata L. leaves, simvastatin, total cholesterol level, CHOD-PAP.