Objective: Cytokines are regulatory proteins which play important role in the regulation of metabolism. Tumor necrosis factor-alpha (TNF-α) is considered as a pro inflammatory cytokines which have been shown to predict the risk of incident of diabetes. The polymorphism at promoter of TNF-α has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of diabetes. We have aimed of present study is to examine the impact of the TNF-α 308 G/A variant allele on various markers of the diabetes and to study its relation with circulating TNF-α in North Indian Population Methods: The -308 G/A gene polymorphism has been studied in 250 diagnosed diabetes subjects (Age 51.62 ± 9.38; BMI 25.05 ± 3.63) and 250 healthy controls (Age 51.72 ± 9.58; BMI 23.17 ± 3.41). This polymorphism of TNF-α 308 G/A was detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha level was also measured by ELISA Results: We have found highly significant in glucose, lipid profile, BMI, Insulin, Insulin resistance except HDL in cases as compare to controls (P < 0.05). Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p > 0.05). On allele contrast, significant association with susceptibility to diabetes was detected with polymorphisms in TNF-α -308G/A, that variant genotype GA+AA (dominant model) (p = 0.045: OR = 1.65: 95% CI = 1.03-2.64) and variant allele (A) (p = 0.024: OR = 1.67: 95% CI = 1.08-2.57) of TNF-α 308G/A gene was significant highly observed in the cases as compared to control group. Moreover TNF-alpha level was observed higher in cases as compared to controls (P < 0.001). Conclusion: Our results suggest that the TNF-α G-308A polymorphism independently associated with susceptibility of diabetes of North Indians population