It has been reported that extracts of stem and leaf of Zanthoxylum ailanthoides (ZLE) possess antioxidative properties. However, the biological importance of the ZLE is not well known. In our preliminary study, it showed that ZLE prepared from 75% alcohol highly contains flavonoids (5.8%). By HPLC analysis, it shows that the ZLE consists of flavonoid glycosides including rutin and hyperoside. We investigate the effects of ZLE on the oxidation of low-density lipoprotein (LDL; d=1.019-1.063 g/mL) and the uptake of lipid in macrophage. Firstly, we explored the effect of ZLE on the oxidation of LDL by employing copper (II) sulfate (CuSO4) as an oxidative inducer. Oxidation was monitored by the formation of conjugated diene and thiobarbituric acid relative substances (TBARS), relative electrophoretic mobility (REM), and fragmentation of apolipoprotein B-100 (Apo B). Our data showed that ZLE reduced the oxidation properties of LDL induced by CuSO4. In addition, ZLE inhibited lipid accumulation in differentiated THP-1 cells treated with ox-LDL involving decreasing the expression of scavenger receptors such as scavenger receptor class AI (SR-AI) and CD36, which belongs to the class B scavenger receptor (SR-B). These results demonstrate the protective effect of ZLE on LDL oxidation and lipid accumulation in macrophage.