Though the rs5219 E23K variant of the KCNJ11 gene is commonly known to be associated with Type 2 diabetes (T2D) in Caucasian and Asian populations, little or none of such findings have been revealed in Nigeria. Hence, this study was aimed to assess the relationship between E23K polymorphic variant of the KCNJ11 gene and T2D in a Nigerian population. A case-control study involving 73 T2D patients and 75 non-diabetic (ND) patients aged above 30 years was conducted. Demographic, clinical, and anthropometric data was collected and the fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), LDL-c and HDL-c were assayed. The KCNJ11 E23K polymorphism was genotyped by RFLP-PCR using BanII restriction enzyme. There was predominance of the mutant A allele as well as the homozygote AA genotype (92.5%) in both T2D and ND patients than the wild G allele and homozygote GG genotype (7.5%). The Engwa GA, et al. 2 Genetics and Molecular Research 17 (1): gmr16039889 heterozygote AG genotype was completely absent in the T2D and ND patients. The AA genotype showed no significant risk of T2D when compared to the GG genotype (OR: 1.183, 95% CI: 0.345-4.059, p= 0.790) in. Genotype frequencies did not violate the Hardy-Weinberg equilibrium in the study population (χ2=0.071; p=0.790). HDL-c was significantly higher (p=0.002) in patients with the GG genotype compared to the patients with the AA genotype. In conclusion, the KCNJ11 E23K polymorphism was not associated with T2D though there was predominance of the mutant A allele in the study population.