The invention relates to application of an MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof. By the invention, the mutual relation between the expression of the MG53 gene and the insulin resistance characteristics is determined; under the condition of the insulin resistance, the expression of the MG53 is obviously raised; the over expression of the MG53 can cause the generation of the insulin resistance; and the defect of the MG53 obviously inhibits all diseases induced by high fat diets, promotes the glucose metabolism, and enhances the insulin sensitivity. Therefore, the MG53 gene can be used as a medical target and used for screening medicines for preventing, relieving and/or treating the insulin resistance, the type II diabetes mellitus and the related diseases thereof. The MG53 gene can also be used as a target gene in the gene treatment and used for designing and preparing the medicines for preventing, relieving and/or treatingthe insulin resistance, the type II diabetes mellitus and the related diseases thereof and/or chemical reagents; and an effective novel approach for the treatment of the insulin resistance, the type II diabetes mellitus and the related diseases thereof is provided.