Recent findings indicate that certain cytokines are capable of interfering with insulin sensitive glucose uptake and induce insulin resistance. To test for the association of IL-10–1082 and IL-6–174 genetic polymorphisms with type 2 diabetes mellitus in Egyptian patients. Participants included 69 cases with type 2 DM (31 males and 38 females) with a median age of 57 years in addition to 98 healthy unrelated controls from the Nile Delta region, Egypt. Compared to controls, cases with type 2 diabetes mellitus showed a highly significant increase in the frequency of IL-10–1082 GG genotype (p<0.001, OR = 11.24); higher frequency of IL-10–1082 G allele (p<0.001, OR = 2.2) with a significantly lower frequency of IL-10–1082 GA genotype (p<0.001, OR = 0.22). On the other hand, the IL-6–174 CC genotype frequency was significantly higher in the diabetic group (p<0.001, OR = 5.41) in contrast to the IL-6–174 GC genotype that showed significantly lower frequency (p=0.005, OR = 0.31) with a non significant differences in either G or C allelic frequencies between diabetic and control groups (p>0.05). Polymorphisms related to IL-10–1082 GG and IL-6–174 CC genotypes may be considered as a risk factor for type 2 diabetes mellitus among Egyptian subjects with a potential impact on family counseling and management.