Inflammation is associated with insulin resistance, atherosclerosis and type 2 diabetes but whether it causes insulin resistance and accelerated atherosclerosis or an epiphenomena of insulin resistance is not clear. Thirty-eight young normoglycemic, non-obese, first degree relatives of type 2 diabetic subjects (FH(+)) and 38 control subjects without family history of diabetes (FH(-)) (age and sex matched), were studied to determine difference in inflammatory markers, insulin resistance and carotid intima-media thickness (IMT). Plasma glucose, insulin (fasting and 2h after 75gm oral glucose) lipids and serum levels of C-reactive protein (CRP), tumour necrosis factor (TNF)-alpha and fibrinogen were measured after an overnight fast of 10-12h. First degree relative group (FH(+)) have higher BMI (p<0.05), composite IMT (p<0.05) and CRP level (p<0.05), however, after adjustment for BMI, the two groups did not significantly differ. Fibrinogen was not significantly correlated with composite IMT in FH(+) group after controlling with BMI. In FH(+) group composite IMT was significantly correlated with systolic blood pressure (p<0.05), LDL-cholesterol (p<0.05), postprandial insulin level (p<0.05) and HOMA-IR (p<0.05) after adjustment of BMI. Thus insulin resistance is a major determinant of atherosclerosis in subjects with high risk of type 2 diabetes showing the strong relationship between inflammation, obesity and insulin resistance.