BACKGROUND: Obesity is among the important healthcare issues in which there is an abnormal increase in body fat because energy intake is higher than energy expenditure. The Tumor Necrosis Factor (TNF)-alpha overexpression in adipose tissue plays important roles in mediating obesity and insulin resistance. "TNF-related apoptosis-inducing Ligand (TRAIL(TNSF10))", which is a member of the TNF family, is expressed as a Type-II Transmembrane Protein with an effect on the development of obesity and diabetes. METHODS: The rs781673405, rs1244378045, rs767450259, rs750556128, rs369143448, rs143353036, and rs759369504 polymorphisms of TRAIL, which were determined to play protective roles against diabetes, were evaluated with the RT-qPZR Method in the present study. RESULTS: It was found that the genotype distribution of TRAIL rs767450259 Polymorphism was significant and the T-Allele had protective effects against diabetic obesity. It was also found that the G-Allele of the rs369143448 Polymorphism had protective roles against diabetic obesity. It was shown that carrying the A-Allele in the rs750556128 Polymorphism might increase the risk of obesity in diabetic patients by 1.3-fold. CONCLUSIONS: The present study makes a significant contribution to the literature data because it is the first to investigate these polymorphisms.