Objective: To investigate the influence of nutrient on the expression of insulin receptor and its related substrate genes in the muscle of mice. Methods:The C57BL/6J mice were divided into 4 groups randomly :(1)Fat,mice on high fat diet;(2)F+G,supplemented with glutamine after 3 month on high fat diet;(3)Gln,high fat with glutamine; (4)Control, normal diet.Each group was fed for 5.5 month. Reverse transcription polymerase chain reaction(RT PCR) was used to determine the mRNA levels of insulin receptor (IR),insulin receptor substrate 1(IRS 1),insulin receptor substrate 2(IRS 2) and phosphatidylinositol 3 kinase(PI 3 kinase).Results: mRNA level of IR,IRS 1,IRS 2,and PI 3 kinase in the mice on high fat diet were lowered to some degree: 81%,63%,59% and 45% that of control. Conclusion: Glutamine can prevent the reduction of the mRNA level of the genes mentioned above in fat group to some extent.The results suggest that nutrient may influence insulin sensitivity of the body through regulation of genes mentioned above.