We examined the association between insulin resistance and adipose tissue compartments in overweight/obese men. Total intra-abdominal, intraperitoneal, retroperitoneal, total subcutaneous, anterior subcutaneous and posterior subcutaneous abdominal adipose tissue (PSAAT) masses (total intra-abdominal fat TIAATM, IPATM, RPATM, TSAATM, ASAATM and PSAATM, respectively) were quantified in 51 overweight/obese men using magnetic resonance imaging (MRI). Total adipose tissue mass (TATM) was also determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. In univariate regression analysis, all fat compartments, with the exception of RPATM, were significantly and positively correlated with the HOMA score. The positive correlation between HOMA score and both IPATM and anterior subcutaneous adipose tissue mass was independent of obesity status. After adjusting total for TATM, only IPATM was significantly correlated with HOMA score (partial r=0.38, P<0.01). In stepwise regression, IPATM was the best predictor of HOMA score. In multivariate regression models including age, obesity status, non-esterified fatty acid (NEFAs) levels, triglycerides and energy expenditure, IPATM remained a significant positive predictor (P<0.05) of HOMA score. In overweight/obese men intraperitoneal AT is the fat compartment that best predicts the degree of insulin resistance. This association appears to be independent of age, total body fat mass and obesity status.