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Introduction Substance P (SP) is a neuropeptide present in enteric neurons, involved not only in the control of intestinal motility, but also in the development of inflammation in the gastrointestinal tract (GIT). The increase in the SP production is associated with the progress of inflammatory process, since SP leads directly to the secretion of cytokines, such as IL-6, IL-8, and TNFα. The GIT is considered the main route of F exposure. Daily, high F concentrations are ingested through dental products, water and food consumption, and in cases of intoxication, important intestinal symptoms are described. Aim To evaluate SP-containing enteric neurons, in the myenteric plexus of the small intestine, since there is no information about F effects on enteric neurons, even with the report of intestinal symptomatology as result of excessive F intake. Thus, we analysed the effects of an acute F exposure by the morphology evaluation of the SP varicosities, which are the axonal portion that concentrates SP. Methods 12 male rats ( Rattus norvegicus – Wistar type) were divided into 2 groups: Control (C) and Acute Dose (AD). The animals received deionized water for 29 days, and at the 30th day they received 0 or 25 mgF/kg orally by gavage. The segments of the small intestine (duodenum, jejunum, and ileum) were collected, and processed for immunohistochemical technique for the SP identification. Morphometric analyses were carried out in 400 varicosities from each animal. The groups were compared by Student’s t -test ( p Results The 3 segments (duodenum, jejunum, and ileum) presented a statistically significant increase (44.6%, 57.1%, and 56.1%, respectively) in the mean value of the areas of the SP myenteric varicosities for DA in relation to C. Conclusion: we may infer that the dose of 25 mgF/kg could lead to an increase in the production of SP, which could impair the intestinal motility, and induce an intestinal inflammatory process.