Aim To investigate the possible mechanism of Curcumin's effect on decreasing plasma lipid and anti atherosclerosis. Methods Wistar rats were fed with high lipid diet 4 weeks to be hyperlipidemic model and then given experimental treatment with Curcumin, XUEZHIKANG and Fenofibrate as positive control drugs. After 3 week's treatment, the levels of total cholesterol (TC) and triglyceride (TG) in the serum and liver were determined. The level of serum high density lipoprotein cholesterol (HDLC), the level of plasma lecithin cholesterol acyltransferase (LCAT) activity , and the levels of postheparin total activity (PHTA), lipoprotein lipase (LPL) and hepatic lipase (HL) activities were all measured. Results The three drugs can decrease the serum TG level significantly, especially the high dosage of Curcumin and Fenofibrate. They can decrease the level of serum TC and low density lipoprotein cholesterol (LDLC), especially XUEZHIKANG and low dosage of Curcumin. The high dosage of Curcumin and Fenofibrate can increase the level of HDLC. Curcumin and Fenofibrate can decrease the level of TC in the liver. The high dosage of Curcumin and Fenofibrate can significantly decrease the level of TG in the liver. Curcumin can increase the LCAT activity in the plasma significantly and decrease the level of free cholesterol (FC)in the plasma. Curcumin and Fenofibrate can increase the level of PHTA. The high dosage of Curcumin can increase the level of HL activity. Curcumin and Fenofibrate can increase the level of LPL activity. Conclusion The results indicate that Curcumin has significant effect on down regulating serum and liver lipids. Meanwhile, it can up regulating the level of plasma lipase avtivities, which may be one of the possible mechanisms of Curcumin's effect on decreasing lipid and anti atherosclerosis.