Abstract The fibronectin type III domain-containing protein 5 (FNDC5) discovered in 2002 has recently gained attention due to its potential role in protecting against obesity. In rat, no data exist regarding FNDC5 production and regulation in the stomach. The aim of the present work was to determine the expression of FNDC5 in the rat stomach and its potential regulation by body composition. The present data shows FNDC5 gene expression in the gastric mucosa. Immunohistochemical studies found FNDC5 immunopositivity in chief cells of gastric tissue. By the use of three different antibodies FNDC5 was found expressed in gastric mucosa and secreted by the stomach. The rate of gastric FNDC5 secretion parallels the circulating levels of FNDC5. The body fat mass increase after intervention with high fat diet coincided with a decrease in the secretion of FNDC5 from the stomach and a diminution in the FNDC5 circulating levels. In summary, the present data shows, for the first time, the expression of FNDC5 in the stomach of rats and its regulation by body composition, suggesting a potential role of gastric FNDC5 in energy homeostasis.