Backround This study aimed to determine the effects of LC n-3 PUFA supplementation on the prevention and treatment of obesity and obesity-related diseases, and to compare the efficiency of different LC n-3 PUFA sources via biochemical and genetic mechanisms in rats. Methods Male Wistar rats were randomized into four study groups, and fed with a standard diet, High Fat Diet (HFD), HFD+%2.5 Fish Oil (FO-HFD) or HFD+%2.5 Krill Oil (KO-HFD) for eight weeks. Food consumption, weight gain, serum glucose, insulin, ghrelin and leptin concentrations, lipid profile, liver fatty acid composition, and FADS1 and FADS2 mRNA gene expression levels were measured. Results Weight gain in each HFD group was significantly higher than control group (p Conclusion LC n-3 PUFAs, especially krill oil, had moderate effects on lipid profile, but limited effects on obesity related parameters, suggesting different effects of different sources on gene expression levels. Further randomized controlled trials are needed to determine the efficacy of different LC n-3 PUFA sources in the prevention and treatment of obesity in humans.