Aim To investigate the influence of total flavonoids of epimedium on adiponectin receptors expression in hyperlipidemia rats and the mechanism of protection in hyperlipidemia rats. Methods 35 male SD rats were randomly divided into two groups: high cholesterol diet group(n=26) and control group(n=9).Rats of high-fat diet group were fed with high-fat diet for 12 weeks,then 26 SD male rats were randomly divided into three groups: model group,high hyperlipidemia group with low dose total flavonoids of epimedium(100 mg/kg) group,hyperlipidemia group with high dose total flavonoids of epimedium(200 mg/kg) group.Serum lipid levels of all rats were measured and the aorta was taken for pathologic analysis.Serum adiponectin was detected by ELISA.The expression of both adiponectin receptor 1(AdipoR1) and adiponectin receptor 2(AdipoR2) on the aorta were analyzed by realtime PCR and Western boltting. Results After 12 weeks of feeding,as compared with full diet group,the levels of triglyceride(TG),total cholesterol(TC) and low density lipoprotein cholesterol(LDLC) in high cholesterol diet groups were significantly increased(P><0.01),which indicated that the hyperlipidemia model was estimated.After 4 weeks' treatment,as compared with high hyperlipidemia model group,the levels of TC,TG in total flavonoids of epimedium groups were obviously lower(P><0.05 or 0.01).Aortic intimal hyperplasia and smooth muscle cells proliferation in rats fed with high cholesterol diet were decreased in high hyperlipidemia with total flavonoids of epimedium groups.As compared with high hyperlipidemia model group,the serum levels of adiponectin with total flavonoids of epimedium were increased(P><0.05),moreover,these changes were more significant in high dose treated group(P><0.05),and the expression of both AdipoR1 mRNA and AdipoR2 mRNA were significantly increased(P><0.05 or 0.01),moreover,the expression of AdipoR1 mRNA were significant in high dose treated group.The expression levels of both AdipoR1 and AdipoR2 protein in total flavonoids of epimedium group were significantly higher than that of hyperlipidemia model group. Conclusion Total flavonoids of epimedium can reduce the levels of serum lipids,but increase the levels of serum adiponectin and the mRNA and protein expression of both AdipoR1 and AdipoR2 on the aorta in hyperlipidemia rats.