Obesity is associated with an increase in plasma leptin levels primarily derived from enhanced expression of the leptin gene in the adipose tissue. Leptin levels and expression are higher in females than males. The main functions of leptin are to decrease food intake and increase sympathetic nerve activity, especially in the brown adipose tissue. The high levels of leptin in obese, female rats suggest leptin resistance. In this article we describe experiments designed to investigate the effect of the intracerebroventricular (i.c.v.) administration of leptin on lumbar sympathetic nerve activity (LSNA) and cardiovascular parameters in female rats fed a low fat diet (control), a high fat diet (obese), or high fat diet followed by a period of food restrictions (reduced). The i.c.v. leptin administration increased LSNA in control rats, but decreased it in obese rats. In weight reduced animals the LSNA response to leptin returned to control levels. The i.c.v. leptin increased the mean arterial pressure in control and wt. reduced rats, but not in obese animals. The heart rate did not respond to leptin in any animal group. These results suggest that obesity decreases the central nervous system (CNS)-mediated lumbar sympathetic nervous and cardiovascular responses to leptin and that these responses recover following food restriction and wt. reduction. We conclude that obesity is associated with a decreased CNS response to leptin leading to a decrease in leptin effects to increase the activities of the autonomic nervous and cardiovascular systems.