Background: Opioid peptides and their receptors are present in the majority of body tissues including gastrointestinal tract. Heroin is one of the opioid derivatives that abuse increasingly today. So far, there is no study on the effect of acute heroin administration on gastric acid and pepsin secretion. Objective: To define the effect of the acute heroin consumption on basal and vagal-stimulated gastric acid and pepsin secretion in rat. Methods: Pure heroin (0.5 mg/kg, ip) was injected to 24 rats. After confirming the signs of heroin effect, animals were anesthetized with sodium thiopental (60 mg/kg, ip). Then, tracheostomy and laparotomy were done, gastric contents were collected by wash out technique over 15 min. The total titrable acid was measured by acid titrator. The pepsin content was measured by Anson method. Vagal electrical stimulation was used to stimulate the secretion of acid and pepsin. Results: A significant increase in both basal and vagotomized state of gastric acid secretion in that group that received heroin, as compared to the control group was shown. Also, in comparison to the control group, electrical stimulation of vagus nerve increased the gastric acid secretion in animals that received heroin. This change, however, was not significant. The basal and vagally stimulated secretion of pepsin was increased, though not significantly, in heroin group in comparison to control group. Conclusion: Basal and stimulated gastric acid and pepsin secretions increase after acute heroin administration in rat.