Leptin, a 16 kDa protein-encoded by the ob gene, is involved in the regulation of food intake, body composition and energy expenditure through a central feedback mechanism. Initially thought to be adipocyte-specific, the ob gene, as well as the leptin receptor, has been found in a variety of other tissues including the stomach. Stomach-derived leptin, mainly secreted in the lumen, remains stable in gastric juice even at pH2. It then enters the intestine where leptin receptors have been identified on the brush border. Recent data also suggest that gut leptin may act locally within the gastrointestinal tract to influence intestinal functions, such as nutrient absorption, and thus have physiopathological implications.