In the last decades, diabetes became one of the most prevalent health problems that threatens people worldwide. Diabetes is defined as a chronic metabolic disorder characterized by elevated blood glucose level (hyperglycemia) that develops as impaired of insulin function or insufficient of insulin production by the pancreas, resulting in insulin deficiency. Type 2 diabetes Mellitus (T2DM) is one type of diabetes resulting from the inability of muscle, fate, liver cells to up take glucose due to insulin resistance and incapability of pancreas to increase insulin secretion to compensate for insulin resistance. T2DM is a multifactorial disease arises from environmental factor, hereditary factor or both of them. Although there are many genes related to T2DM, the transcription factor 7-like-2 gene (TCF7L2) rs7903146 (A/T) and rs4506565 (C/T) polymorphism are two of the most susceptible genes to T2DM discovered to date, with the contribution to the disease through the Wnt/β-catenin signaling pathway affecting pancreatic islet development. This study investigates and analyze the correlation of TCF7L2 gene polymorphisms and their association with type 2 diabetes for Egyptian patients. The study included 100 blood samples equally divided into two groups: 50 patients with T2DM and 50 normal healthy controls.  All Genotypes of rs7903146 (A/T) SNP in theTCF7L2 gene were evaluated by RFLP- PCR using RSA1 restriction enzyme. And all Genotypes of rs4506565 (C/T) were evaluated by ARMS-PCR. Both of them showed non-significant differences, and no association with T2DM.