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Shanshan Xie,1,2 Wenguo Fan,2,3 Hongwen He,2,4 Fang Huang1,2 1Department of Pediatric Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 3Department of Anesthesiology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Oral Anatomy and Physiology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Fang Huang; Hongwen HeGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People’s Republic of ChinaTel +86 20 87330570Fax +86 20 87330709Email hfang@mail.sysu.edu.cn; 497642565@qq.comAbstract: Melatonin is a pleiotropic hormone synthesized and secreted mainly by the pineal gland in vertebrates. Melatonin is an endogenous regulator of circadian and seasonal rhythms. Melatonin is involved in many physiological and pathophysiological processes demonstrating antioxidant, antineoplastic, anti-inflammatory, and immunomodulatory properties. Accumulating evidence has revealed that melatonin plays an important role in pain modulation through multiple mechanisms. In this review, we examine recent evidence for melatonin on pain regulation in various animal models and patients with pain syndromes, and the potential cellular mechanisms.Keywords: melatonin, pain, cellular mechanisms