Abstract: Natto lyophilized powder and red yeast rice powder was the raw material. Female Kunming mice were inoculated with fat emulsion to establish a model of hyperlipidemia. According to the level of body weight,mice were equally divided into eight groups,seven of which were high-fat mice and the other group were normal mice. Different concentrations of the compound(200 mg/mL natto lyophilized powder,100 mg/mL red yeast rice powder,100 mg/mL natto lyophilized powder+25 mg/mL red yeast rice powder,100 mg/mL natto lyophilized powder+100 mg/mL red yeast rice powder,200 mg/mL natto lyophilized powder+25 mg/mL red yeast rice powder,200 mg/mL natto lyophilized powder+100 mg/mL red yeast rice powder)which formulated into different doses were gavage according to the situation of experimental groups. Morphological and weight changes in mice were observed during the gavage period. After the gavage period,organ index in mice including liver to body ratio and fat coefficient,serum lipid levels and liver cholesterol(TC)and triglyceride(TG)content were determined. The results showed that the high dose of compound(200 mg/mL natto lyophilized powder+100 mg/mL red yeast rice powder)could significantly reduce the level of TC(p<0.01)and TG in serum(p<0.05),increase the level of high density lipoprotein-cholesterol(HDL-C)(p<0.01),and reduce the level of TC and TG in mice liver significantly(p<0.05),and play a lipicl-lowering effect. Therefore,the compound of natto lyophilized powder and red yeast rice powder could play a synergistic effect in reducing lipid level and jointly promote lipid-lowering activity in mice.