It has been reported that phospholipid transfer protein (PLTP) is an independent risk factor for human coronary artery disease. And metabolic tissues are important contributors to the systemic pools of PLTP protein. Consistently, PLTP mass and activity have been found to be elevated in the plasma of type 2 diabetes mellitus (T2DM) and obese patients. In this review, we summarized the recent progresses made in the PLTP research field and focused on the complexity of the implication of PLTP in obesity, insulin resistance and T2DM.