To observe the effect of blood-letting puncture therapy on NO, ET-1 and blood lipid in rats with hyperlipidemia, and explore its therapeutic effect and mechanism in treating hyperlipidemia. Methods:A total of 32 male SD rats were randomly divided into 4 groups, which are control group, model group, blood pricking group and medical group. Except for the control group, the other three groups were made into hyperlipidemia models by high fat diet. After modeling, rats in control group received no treatment. The model group was fixed to receive blood-letting puncture therapy on the superficial vein of the rats hind leg, 0.3-0.5 mL each time, 2 times a week.To observe the levels of TC, TG, HDL-C, LDL-C, NO and ET-1. Results:Comparing to the control group, the level of TC, TG, LDL-C, ET-1 of the model groups significantly increased, and the level of HDL-C and NO content in the model groups significantly decreased with significant difference (P<0.01). Comparing to the control groups, the levels of TC, TG, LDL-C, ET-1 content in the other groups decrease, and the levels of HDL-C and NO content in the blood-letting group and medicine group increased, and the difference is significant (P<0.05，P<0.01). Conclusion:Blood-letting puncture therapy can correct lipid metabolism abnormalities. Besides, by inhibiting the increase of ET-1 content and maintain vascular endothelial cell balance, it can reduce and delay endothelial cell injury.