【Abstract】 Background D-Serine is a main endogenous modulator of N-methyl-D-aspartate (NMDA) receptor at the glycine binding site. It is synthesized and secreted by the glial cells and neurons. In vivo, it is synthesized via racemization of serine racemase and removed by D-amino acid oxidase. There are many kinds of chronic pain, whose causes are complicated. Previous studies have confirmed that chronic pain is related to the long-term functional changes in peripheral and spinal levels, leading to the formation of central sensitization which NMDA receptor plays an important role in. D-serine, a main endogenous ligand of NMDA receptor, is also important in the development and progression of chronic pain. Objective To understand the physiological function and mechanism of action of D-serine, and its role in chronic pain. Content To review the recent advances of D-serine in chronic pain and the therapeutic value. Trend regulatory system of D-serine may provide a new way in the treatment of chronic pain.