Background: Many loci were found to be associated with type 2 diabetes mellitus (T2DM) risk as single nucleotide polymorphism (SNP) at the transcription factor 7-like 2 gene (TCF7L2) locus on chromosome 10q (rs7903146) [C/T]. Aim: Estimation of the association of this gene polymorphism with T2DM and its complications in Egyptian population. Patients and Methods: This study was done, using 90 Egyptian T2DM patients and 100 controls. This polymorphism was genotyped by conventional PCR. Measurement of blood glucose, glycated hemoglobin (HbA 1c), lipid profile, and microalbuminuria were performed for the study subjects using standard methods. Body Mass index and fundus examination for detection of diabetic retinopathy were also done. Results: The genotype and allele frequencies in TCF7L2 rs7903146 were nearly the same in the patient and control groups (P > 0.05).Odds Ratio for the high risk allele (T) of (rs7903146) was (OR) = 0.97 with 95% confidence interval (CI) from 0.61 to 1.54 with the P = 0.9. Conclusion: These data suggest that the TCF7L2 SNP rs7903146 may not significantly contribute to T2DM susceptibility in Egyptian population.