This study was carried out to evaluate the effects of omega-3 fatty acid administration on markers of insulin resistance, lipid concentrations, biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy (DN). This parallel randomized double-blind placebo-controlled clinical trial was performed among 60 patients with DN. Patients were randomly allocated into two groups to receive either 1000mg/day omega-3 fatty acid from flaxseed oil (n=30) or placebo (n=30) for 12 weeks. Fasting blood samples were taken at the onset of the study and 12 weeks after supplementation to assess glycaemic status, lipid concentrations, biomarkers of inflammation and oxidative stress. After 12 weeks of treatment, patients who consumed omega-3 fatty acid supplements compared with the placebo had significantly decreased serum insulin levels (-39.6±10.8 vs.-7.2±8.4pmol/L, P=0.001), homeostasis model of assessment-estimated b cell function (HOMA-B) (-30.2±11.2 vs.-1.5±6.8, P=0.03) and improved quantitative insulin sensitivity check index (QUICKI) (+0.01±0.004 vs.+0.002±0.004, P=0.03). Additionally, compared with the placebo, omega-3 fatty acid administration led to a significant reduction in serum triglycerides (-19.8±8.8 vs.+12.6±10.2mg/dL, P=0.01) and VLDL-cholesterol concentrations (-4.0±1.8 vs.+2.5±2.0mg/dL, P=0.01). Supplementation with omega-3 fatty acid had no significant effects on other lipid subfractions, biomarkers of inflammation and oxidative stress compared with the placebo. In addition, within-group differences revealed significant reductions in serum insulin (P=0.001), HOMA-IR (P=0.004), HOMA-B (P=0.01), serum triglycerides (P=0.03), VLDL- (P=0.03), total- (P<0.001), LDL- (P=0.002), total-/HDL-cholesterol ratio (P=0.001), blood urea nitrogen (P=0.04), and significant increases in QUICKI (P=0.001) and nitric oxide (P=0.005) and total antioxidant capacity concentrations (P=0.02) in the omega-3 fatty acid group. Our findings indicated that omega-3 fatty acid administration for 12 weeks among DN patients had favorable effects on insulin levels, HOMA-B, QUICKI, serum triglycerides and VLDL-cholesterol; however, it did not influence biomarkers of inflammation and oxidative stress.