Diabetic dyslipidemia in type 2 diabetes (T2DM) is characterized by elevated levels of triglycerides (TG), decreased levels of high density lipoprotein-cholesterol (HDL-C), elevated levels of low density lipoprotein-cholesterol (LDL-C), and the predominance of small and dense LDL particles (sdLDL). The mechanism underlying diabetic dyslipi-demia remains unclear. Insulin resistance is believed to be an important determinant. Mechanisms underlying insulin resistance-induced diabetic dyslipidemia seem to be related to apolipoprotein CIII (ApoCIII), a known inhibitor of lipoprotein lipase. The concentration of very low density lipoprotein1 (VLDL1) with a higher TG content and abundant ApoCIII was found to be significantly elevated in patients with T2DM. Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia. Herein, this paper will review recent advance in pathophysiology of diabetic dyslipidemia and the role of ApoCIII in this condition, with focus on describing a novel drug volanesorsen as potential treatment strategy.