Enterostatin is a pentapeptide released from its precursor protein procolipase, which is synthesized in the exocrine pancreas and gastric mucosa. As central injection of enterostatin has potent effects on feeding, we hypothesized that the procolipase may also be expressed in the brain. We confirmed the presence of preprocolipase gene expression in amygdala by reverse transcription-polymerase chain reaction and Northern blot analysis and of protein expression by Western blots. Immunohistochemical analysis using antibodies for procolipase and enterostatin identified their immunoreactivity (IR) in rat brain. Procolipase IR was present in the cytoplasm of paraventricular, amygdala, and the dorsal thalamus nucleus. Enterostatin IR was evident in the fibers of the dorsal thalamus and arcuate nucleus. In vivo injection of enterostatin antibody into rat amygdala increased food intake. These data suggest that procolipase and enterostatin are synthesized within specific regions of the brain that function in the regulation of food intake centrally.