AbstractAim: to evaluate if a supplementation with n‐3 PUFAs at high doses could give a regression of the condition of impaired glycemia. Methods: we enrolled 281 overweight/obese patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT); 138 subjects were randomized to n‐3 PUFAs group, 1 g three times a day, and 143 to placebo for 18 months. We assessed at baseline, and after 9, and 18 months: circumferences, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), HOMA‐index, lipid profile. At baseline and at the end of the study, all patients underwent an oral glucose tolerance test (OGTT). Results: we observed a decrease of glycemia and HOMA‐IR with n‐3 PUFAs, compared to baseline, and to placebo. Fasting plasma insulin decreased with n‐3 PUFAs and increased with placebo. HDL‐cholesterol increased after 18 months of n‐3 PUFAs, while triglycerides decreased compared to baseline and to placebo. After OGTT performed at the end of the study, more patients returned to a condition of euglycemia with n‐3 PUFAs compared to placebo. Conclusions: n‐3 PUFAs were effective in reducing glycemia in patients affected by IFG or IGT and seem to be helpful to slow the development of type 2 diabetes mellitus. © 2016 BioFactors, 42(3):316–322, 2016