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For diabetic patients, control of diabetic vascular complications (DVC) such as diabetic nephropathy (DN), neuropathy, and retinopathy is very important. One of the causes of DVC is abnormal protein kinase C (PKC) activation caused by diacylglycerol (DG) synthesized through the de novo pathway. However, several trials to develop medicines targeting PKC for DVC have failed. Diacylglycerol kinase (DGK) can attenuate PKC activity by converting DG to phosphatidic acid (PA), suggesting that activation of DGK may improve DVC. Indeed, we found that d-α-tocopherol (vitamin E; VtE) improved DN via activation of DGKα. These facts indicate a balance between two lipid messengers, DG and PA, which is important for controlling DVC, and DGK is a good candidate for a pharmaceutical target of diabetes and DVC. In this chapter, our research on the functions of DGK related to diabetes and DVC and the mechanism …