Background:There are many report about anti-infi ammatory potentials of melatonin on experimental colitis and ulcerative colitis in human. So we aimed to evaluate the anti-infi ammatory mechanism of melatonin on DSS induced colitis with and without sleep deprivation by gene expression after melatonin treatment. Methods: We used the 5 groups of C57BL/6 mice. Group I: control, Group II: 2% DSS induced colitis for 7days, Group III: 2% DSS induced colitis and melatonin (10mg/kg) treatment, Group IV: 2% DSS induced colitis with sleep deprivation(SD, 20hr/d) and Group V: 2% DSS induced colitis with SD and melatonin treatment. RNA was isolated from the colon of mice to analyze by microarray. We confi rmed signifi cant changes of expression of important genes by RT-PCR. Based on microarray result, we planned to perform immunohistochemical staining and Western blotting. Results: Sleep deprivation worsens body weight reduction of mice and exacerbate the severity of colonic infi ammation. Administration of melatonin reduced the rate of weight loss and severity of mucosa injury compared with saline injection group. 68 genes were signifi cantly changed by 2% DSS, sleep deprivation and melatonin in microarray. In RT-PCR there are signifi cant change of adipoq gene, which are related with adiponectin protein. We also confi rmed adiponectin expression by melatonin injection using immunohistochemical stain and Western blotting. Conclusions: Sleep deprivation acts as an aggravating factor, whereas melatonin acts as an improving factor of infi ammation. Besides sleep control, Melatonin has potent anti-infi ammatory effects on colonic mucosa. It is known that adiponectin also had an anti-infi ammatory effects by inhibiting Nuclear Factor-kappa B, TNF-a and IL-6 and inducing anti-infi ammatory cytokines such as IL-10, and IL-1 receptor antagonists. Adiponectin mRNA was decreased in infi amed colonic mucosa of murine colitis and restored by melatonin. This study showed melatonin directly affect mucosal healing and indirectly modulate adiponectin pathway