Paraoxonase1 (PON1) is an enzyme that associated with high density lipoprotein (HDL), and demonstrating esterase and lactonase activity. The PON1 has a role in a variety of inflammatory conditions, metabolism of oxidized lipids and detoxifying of organophosphorus insecticide substrate. The aim of this study was to investigate the effects of Tanacetum parthenium methanolic extract (TPME) on arylesterase activities in CCl4 injected rats. Experiments were conducted in five groups of normal, CCl4 and different dose of TPME (TPME40, 80 and120mg/kg) rats. Two weeks after receiving the different dosages of TPME, CCl4 were administered intraperitoneally on the 16th day.after 48h blood samples were taken from animals and HDL level, arylesterase activity of PON1 enzyme and standardized activities of arylesterase (ARE/HDL) were measured in rats. Relative changes in serum HDL and arylesterase activities were compared between the groups. Administration of TPME significantly increased serum arylesterase activities and HDL level in CCl4 treated groups compared to untreated ones. These essential effects may be due to the presence of natural antioxidants such as phenolic compounds in the TPME. Methanolic extract of T.parthenium may be useful in decreasing the symptoms of diseases resulting from the low activity of ARE.