This work is therefore designed to investigate the antiulcer potential of Setaria megaphylla ethanol root extract. The ethanol root extract (150, 300, 450 mg/kg) was investigated for indomethacin, ethanol and histamine- induced ulcers in rats using standard procedures. The extract caused a progressive, dose-dependent and statistically significant (p<0.05 - 0.001) decline in ulcer index of the rats pretreated with the extract and a dose-dependent progressive preventive ratio. The observed effect of the extract (150 - 450 mg/kg) was weak compared to the standard drugs, cimetidine 100 mg/kg and propranolol 40mg/kg respectively used in the indomethacin and ethanol models, but the 450 mg/kg dose of the histamine model had a higher effect than the standard drug, cimetidine 100 mg/kg. The results of this study revealed that the ethanol root extract of S. megaphylla possesses anti-ulcer effects from its phytochemical components.