Leptin preserves lean tissue, but decreases adipose tissue by increasing lipolysis and/or inhibiting lipogenesis. The sympathetic nervous system (SNS) is a primary regulator of lipolysis but it is not known if leptin increases norepinephrine turnover (NETO) in white adipose tissue. In this study we examined the effect of leptin administered either as a chronic physiologic dose, 40 µg/d for 4 days (from intraperitoneal miniosmotic pumps) or as an acute injection into the third ventricle (1.5 µg injected twice daily for 2 days) on NETO and the size of brown and white fat depots in male Sprague-Dawley rats. NETO was determined from the decline in tissue NE during 4 hours following administration of the NE synthesis inhibitor, -methyl-para-tryrosine. The centrally injected leptin-treated animals demonstrated more dramatic reductions in food intake, body weight, fat pad size, and increase in NETO compared to the peripherally infused animals. Neither route of leptin administration caused a uniform increase in NETO across all fat pads tested and in both treatment conditions leptin decreased the size of certain fat pads independent of an increase in NETO. Similar discrepancies in white fat NETO were found for rats pair-fed to leptin treated animals. These results demonstrate that leptin acting either centrally or peripherally selectively increases sympathetic outflow to white fat depots and that a leptin-induced change in fat pad weight does not require an increase in NETO.