Background Type two diabetes (T2DM) is characterized by insufficient insulin production and secretion. Additionally, the body develops insulin resistance which affects 90–95% of diabetics. Complex cytokines, receptors, genetic pathways, and the immune system are involved in T2DM. Interleukin-18 (IL-18) is one of the inflammatory cytokines associated with Type 2 diabetes. Environmental and genetic variables, including genetic polymorphisms, can increase T2DM risk and its consequences. Single nucleotide gene polymorphisms (SNPs) are important risk factors for diabetes that can be used to find the disease early and treat it better. Objective This study aimed to determine the levels of IL-18 in the serum of Iraqi patients with Type 2 diabetes mellitus, as well as the effect of IL-18 SNP rs1946518 (-607 G/T) in the etiology of T2DM. Materials and Methods This study involved 100 T2DM patients (52 males and 48 females) who visited Al-Karamah Teaching Hospital and Baghdad Teaching Hospital. 52 Iraqi control subjects (26 males and 26 females) were included. A sandwich enzyme-linked immunosorbent assay was used to quantify the IL-18 serum levels of 48 patients and 40 healthy controls. The genotype of IL-18 was determined using Real-time (RT) Taqman PCR. Results According to age, the current study revealed a non-significant correlation (p-value > 0.05) among the studied groups. IL-18 levels in the T2DM group were substantially greater than in the healthy control. In addition, the genotyping frequencies revealed that the frequency of TT genotyping was higher in T2DM group than in healthy control (80% versus 66.7%, OR: 2.0), whereas the frequency of GT genotyping was lower in T2DM than in healthy persons (20% versus 33.3%, OR: 0.5). Conclusion: This Iraqi’s novel study indicated that IL-18 and it’s SNP(rs1946518) contributes to the pathophysiology of Type 2 diabetes mellitus.