Abstract: Objective To study plasma tumor necrosis factor α(TNF α) level and its relationship with insulin resistance in familial type 2 DM. Methods Plasma TNF α were determined by RIA in 32 familial type 2 DM patients, their 37 non diabetic first degree relatives and 40 healthy control subjects. Results Plasma TNF α was significantly higher in familial type 2 DM patients[(1.19±0.21)μg/L] than in healthy control subjects[(1.00±0.18)μg/L]( P <0.05), with no significant difference found between the non diabetic first degree relatives [(1.01±0.28)μg/L] and healthy control ( P >0.05). Regression analysis indicated that TNF α was inversely related to ISI and was a significantly independent contributor to variations in ISI. 39% of the variance in ISI was explained by TC, body mass index(BMI)and TNF α. Conclusion The finding of an association between high plasma levels of TNF α and insulin resistance suggests that TNF α may be involved in the pathophysiology of insulin resistance in familial type 2 DM patients.