Abstract: AIM:To explore total flavonoids of epimedium (TFE) on nitric oxide (NO) and nitric oxide synthetase (NOS) in aorta in hyperlipidemic rats and to explore the possible mechanism of anti-atherosclerosis (AS). METHODS: According to body weight, 35 male Sprague Dawley (SD) rats were randomly divided into the full diet group (n=9) and the high-fat (HF) diet group (n=26) that was fed a HF diet for 12 weeks. Serum lipid levels were then measured. An ideal experimental rat model of hyperlipidemia was made when lipid level was higher in the HF diet group. According to body weight, 26 male SD rats were then randomly divided into three groups, namely, model group, low-dose ［100 mg/(kg·rat)］ TFE group and high-dose ［200 mg/(kg·rat)］ TFE group. After 16 weeks of feeding, serum lipid (TG, TC, LDL-C, HDL-C) level was measured. Triglycerides (TG) were measured by CHOD-PAP method, total cholesterol (TC) was detected by CHOD-PAP, and low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by selectivity precipitation method. NO was determined by nitric acid reductase method, and iNOS and tNOS were determined by catalytic method (cNOS activity was obtained by subtracting iNOS activity from the total NOS activity). RESULTS: After 12 weeks of feeding, compared with those in the full diet group, the levels of TG, TG,and LDL-C in HF diet group significantly increased (P<0.01). After a 4-week treatment, compared with the model group, levels of TC and TG in TFE group were obviously lower (P<0.05 or P<0.01). The model group showed lower NO and cNOS concentrations (P<0.05 or P<0.01). The level of NO and cNOS of in the TFE group increased significantly (P<0.05, P<0.01). CONCLUSION: TFE reduces blood lipid levels and elevates NO and cNOS levels of vascular aorta in hyperlipidemic rats.