Abstract: Objective To explore the effects of docosahexaenoic acid (DHA) on palmitate-induced insulin resistance in C2C12 cells.Methods Differentiated C2C12 myotubes were used.The gene expression of inflammatory cytokine and insulin signaling pathway were evaluated by quantitative polymerase chain reaction (qPCR) and Western blot.And glucose uptake was measured by [3H]-2DG uptake.The levels of reactive oxygen species (ROS) were evaluated by DCF fluorescence.And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured with a glutathione assay kit.Results Palmitate-induced cellular insulin resistance was clarified by reduced [3H]-2DG uptake and impaired gene expression of insulin signaling pathway (GLUT4,p-IR3 and p-IRS-1).DHA decreased the expression of palmitate-caused pro-inflammatory cytokines (MCP-1,IL-6 and iNOS) and oxidative stress and increased the gene expression of insulin signaling pathway (Glut4 and p-IRβ).Conclusion Palmitateinduced insulin resistance is accompanied by elevated pro-inflammatory cytokines,oxidative stress and impaired gene expression of insulin signaling pathway.And DHA decreases inflammation and oxidative stress and increases glucose uptake in C2C12 cells.Thus DHA attenuates palmitate-induced insulin resistance.