OBJECTIVE To analyze the putative interest of oligofructose (OFS) in the modulation of food intake after high-fat diet in rats and to question the relevance of the expression and secretion of intestinal peptides in that context. METHODS Male Wistar rats were pretreated with standard diet or OFS-enriched (10%) standard diet for 35 days followed by 15 days of high-fat diet enriched or not with OFS (10%) treatment. Body weight, food intake, triglycerides, and plasma ghrelin levels were monitored during the treatment. On day 50, rats were food-deprived 8 hours and anesthetized for blood and intestinal tissue sampling for further proglucagon mRNA, glucagon-like peptide (GLP)-1, and GLP-2 quantification. RESULTS The addition of OFS in the diet protects against the promotion of energy intake, body weight gain, fat mass development, and serum triglyceride accumulation induced by a high-fat diet. OFS fermentation leads to an increase in proglucagon mRNA in the cecum and the colon and in GLP-1 and GLP-2 contents in the proximal colon, with consequences on the portal concentration of GLP-1 (increase). A lower ghrelin level is observed only when OFS is added to the standard diet of rats. CONCLUSIONS In rats exposed to high-fat diet, OFS is, thus, able to modulate endogenous production of gut peptides involved in appetite and body weight regulation. Because several approaches are currently used to treat type 2 diabetes and obesity with limited effectiveness, dietary fibers such as OFS, which promote the endogenous production of gut peptides like GLP-1, could be proposed as interesting nutrients to consider in the management of fat intake and associated metabolic disorders.