Leukoaraiosis (LA) is a nerve conduction fiber demyelinating disease in the brain white matter resulted from diffuse cerebral ischemia caused by cerebral small vessel disease (SVD). It is an early sign of brain damage. Nitric oxide (NO) is an endothelium-derived relaxing factor, and its production is catalyzed by nitric oxide synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. Increase of ADMA reduces the production of NO, which then leads to vascular endothelial dysfunction. Dimethylarginine dimethylaminohydrolase (DDAH) is a main metabolic enzyme of endogenous ADMA, and key factor determining the plasma content of ADMA. ADMA/DDAH pathway may affect LA through the mechanism of vascular endothelial damage.