TCF7L2 is a Wnt signaling-associated transcription factor expressed in several tissues, including gut and pancreas. Wnt signaling plays an important role in β-cell proliferation and insulin secretion and influences synthesis of glucagon-like peptide-1 (GLP-1) in intestinal L-cells. The association between TCF7L2 gene variants and type 2 diabetes mellitus(T2DM) has been confirmed by the genome-wide association study (GWAS) and a lot of other studies in different ethnic groups. Single nucleotide polymorphisms and alternative splicing of TCF7L2 affect both the pancreatic β cell function and insulin resistance. Further study will provide new pathways for the prevention and treatment of T2DM.