Oxidatively modified low density lipoprtein (LDL) plays an important role in atheroslerosis (AS) development. To investigate the role of neferine (Nef) in anti-LDL oxidation and foam cell formation, the lipoprotein was derived and subjected to three different treatments: N-LDL (normal LDL), Cu(2+) +LDL and Cu(2+)+Nef+LDL. The LDLs were put at 25℃ for 24 h and the thiobarbituric acid reactive substance (TBARS) values were determined. They were 0. 57 ±0. 02, 6.01±0. 22 and 2. 26±0. 13 nmol/mg protein, respectively. The difference was very significant (P<0.01) for each two groups by t test. Mouse peritoneal macrophage (MΦ) were exposed to 50 μg protein/ml of Cu(2+) + LDL and Cu(2+)+Nef+LDL at 37℃ for 60 h. The tryglyceride (TG) and total cholesterol (TC) content in Mad were assayed. The results showed that Cu(2+) + LDL was more efficient than Cu(2+)+Nef+LDL in stimulating lipid accumulation in MΦ(P <0. 001). The study demonstrated that Nef could inhibit Cu(2+)-mediated LDL oxidation and thereby inhibiting macrophage-derived foam cell formation.