To explore the association of TNF-α-308 and IFN- γ +874 genetic polymorphisms with type 2 diabetes mellitus (DM) in Egyptian cases. Participants included 207 cases with type 2 DM, 93 males and 114 females. Their mean age was 57 years. They were compared to a control group of 212 healthy unrelated subjects from the same locality. DNA was amplified using PCR with sequence specific primers for detection of polymorphism related to TNF-α-308 (G/A) and IFN-γ+874 (A/T). The combined homozygote pattern of TNF-α-308 (AA) and IFN-γ+874 (A/A) was significantly higher in diabetic cases versus controls (p=0.023) that was manifest (although non-significant) among complicated, uncontrolled cases and cases with marked insulin resistance. Polymorphism related to TNF-α-308 AA and IFN-γ+874 AA may be considered as a genetic biomarker for type 2 DM in Egyptian subjects with potential impact on family counseling and management.