To evaluate whether Orthosiphon stamineus (OS) reduces appetite and fat deposition, food intake and visceral fat mass following treatment with OS (450 mg/kg/day, per oral) for 2 weeks in Sprague-Dawley (SD) rats were measured. Hypothalamic neuropeptides associated with appetite regulation was also analyzed. Two weeks of OS treatment reduced food intake and visceral fat mass compared to saline-treated SD rats. OS treatment for 2 weeks elevated the expression of proopiomelanocortin (POMC) in the hypothalamus, whereas neuropeptide Y (NPY) expression was decreased, which may be associated with the elevation of plasma leptin concentration in OS-treated rats. Methanol and butanol extracts of OS increased leptin mRNA expression in 3T3-L1 cells in dose-dependent manner. Acute study showed intraperitoneal injection of various concentrations of OS increased POMC expression in the hypothalamus, whereas NPY expression decreased dose-dependently. These results suggest that OS reduces appetite, which may have resulted from the increased expression of POMC and decreased expression of NPY in the hypothalamus in association with the elevation of leptin. OS could be a medicinal food applicable for body weight control.