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The anti-ulcer and other gastrointestinal effects of the methanol extract and fractions of Cucumis metuliferus were investigated in rats and mice. Ethyl acetate (EAFCM), butanol (BFCM) and water (WFCM) fractions obtained from the methanol extract of Cucumis metuliferus (MECM) were screened for anti-ulcer activity. The anti-ulcer effect was investigated on gastric ulcers induced by absolute ethanol, hypothermic-restraint stress and indomethacin in rats. The median lethal dose (LD50) of the extract and its fractions were determined in mice by the oral route using technique of Locke. The effect of MECM and fractions on gastrointestinal propulsive movement in mice was investigated. Their effects on the rabbit jejunum and guinea pig ileum were also carried out. The results revealed that the extract and its fractions at doses up to 5000 mg/kg showed no signs of toxicity or death. The extract and fractions at doses of 100 - 400 mg/kg significantly (P< 0.05) reduced the ulcer indices in a dose-related manner. MECM and fractions produced a significant (P< -0.05) inhibition of gastrointestinal tract motility on the rabbit jejunum in a dose-dependent manner. MECM and fractions produced a concentration-dependent relaxation of rabbit jejunum. MECM and fractions did not show any effect on the guinea pig ileum. However the contractile effect produced by histamine was attenuated by the extract and fractions, contractile effect of acetylcholine on guinea pig ileum was not attenuated. Preliminary phytochemical analysis showed presence of flavonoids, alkaloids, saponins, carbohydrates, steroids, trepenoid, anthraquinones and cardiac glycosides. Put together, the results of the study showed that Cucumis metuliferus contain bioactive ingredients which have protective effects against gastroerosive ulcers induced by ethanol, stress and indomethacin.