Objective: Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of beige fat cells in WAT prompted us to investigate whether melatonin is a brown-fat inducer. Methods: We used wild-type C57BL6 mouse. At 5 wk of age, mice were subdivided into two groups, each composed of four mice: control and those treated with cutaneous melatonin using osmotic pump (10 mg/kg/day) for 6 wk. Results: Melatonin induced browning of inguinal WAT. Hematoxylin-eosin staining showed patches of brown-like adipocytes in inguinal WAT. Melatonin sensitized the thermogenic effect of acute cold exposure. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1), other thermogenic genes and beige adipocyte markers in extracts from beige inguinal areas. Melatonin regulates this process, at least in part, by enhancing adipose tissue PGC-1a protein levels independently of mRNA expression. Melatonin also acts on human subcutaneous white adipocytes in culture to stimulate UCP1 expression and a broad programof brown-fat-like development. Conclusion: These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in normal mice. These results suggest that targeting melatonin and its downstream signaling represents a therapeutic approach to treat obesity and type 2 diabetes.