Background: Information is lacking on the potential effect of nҀ3 polyunsaturated fatty acids (PUFAs) on the adipose tissue of patients with type 2 diabetes. Objective: We evaluated whether nҀ3 PUFAs have additional effects on adiposity, insulin sensitivity, adipose tissue function (production of adipokines and inflammatory and atherogenic factors), and gene expression in type 2 diabetes. Design: Twenty-seven women with type 2 diabetes without hypertriglyceridemia were randomly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil (1.8 g nҀ3 PUFAs) or placebo (paraffin oil). Results: Although body weight and energy intake measured by use of a food diary were unchanged, total fat mass (P 0.019) and subcutaneous adipocyte diameter (P 0.0018) were lower in the fish oil group than in the placebo group. Insulin sensitivity was not significantly different between the 2 groups (measured by homeostasis model assessment in all patients and by euglycemichyperinsulinemic clamp in a subgroup of 5 patients per group). By contrast, atherogenic risk factors, including plasma triacylglycerol (P 0.03), the ratio of triacylglycerol to HDL cholesterol (atherogenic index, P 0.03), and plasma plasminogen activator inhibitor-1 (P 0.01), were lower in the fish oil group than in the placebo group. In addition, a subset of inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil, but not the placebo, treatment. Conclusions: A moderate dose of nҀ3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes. Some adipose tissue inflammation-related genes were also reduced. These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue. This trial was registered at clinicaltrials.gov as NCT0037.Am J Clin Nutr 2007;86:1670 -9.