Abstract: Present study aims to evaluate the effect of proso millet prolamin(PMP) on cholesterol(metabolism) in mice,by comparing the concentration of plasma total (cholesterol),high-density lipoprotein cholesterol(HDL-c) with triglyceride of mice given the diets containing casein,soy protein isolated or(PMP(supplemented) with 1.82%Lys and 0.23%Trp).The mice fed with PMP diet showed the highest(HDL-c) content significantly(P<0.05) and the lowest atherogenic index among three groups.In vitro,(PMP couldn't) inhibit the activity of 3-hydroxy-3-methylglutaryl-coenayme A(HMG-CoA) reductase,and the synthesis of cholesterol directly.On the basis of the linear regression analysis,the content of sulfur-containing amino acids,hydrophobic amino acids,the ratio of Met to Gly(Methionine/Glycine) of PMP were important factors in modulating the metabolism of serum cholesterol in mice.