Background: Hyoscine N-butylbromide (Buscopan) is clinically used as an anticholinergic antispasmodic for the treatment of abdominal cramping or visceral pain associated with cramps. Objectives: we aimed to study the effect of pretreatment by a single injection of various doses of Hyoscin N-butylbromide (HBB) (1mg/Kg, 2.5mg/Kg and 5mg/Kg), on changes in gastric contents in pyloric ligated rats receiving indomethacin in a dose of 100mg/Kg i.p, and on gastric ulcer formation induced in rats by the same dose of indomethacin and subjected to restraint stress. Materials and Methods: This study was conducted on 60 adult male albino rats, divided into two equal categories, which were further divided into five equal subgroups. Results: Administration of HBB in doses of 1mg/Kg (i.p) to rats subjected to restraint stress and indomethacin administration in a dose of 100mg/kg led to insignificant decrease in the gastric ulcer index relative to the group received indomethacin and subjected to restraint stress with a protection ratio of (3%). Administration of HBB in doses of 2.5mg/Kg and 5mg/Kg (i.p) to rats subjected to restraint stress and indomethacin administration in a dose of 100mg/kg led to a significant decrease in the gastric ulcer index relative the group received indomethacin and subjected to restraint stress with a protection ratio of 60.46% and 66.41% respectively. Administration of HBB in doses of 1mg/Kg, 2.5mg/Kg and 5mg/Kg (i.p) to pyloric-ligated rats led to a significant decrease in gastric juice volume, acid concentration and the total acid output compared to the group receiving indomethacin. Conclusion: Intraperitoneal administration of HBB in doses of 1mg/Kg, 2.5mg/Kg and 5mg/Kg to rats in a dose-dependent manner led to a prophylactic effect against stress induced gastric ulcers, with a protection ratio of 3%, 60.46% and 66.41%  respectively.