Background The leaf of Zehneria scabra is traditionally used for the management of diarrhea in Ethiopia. Its use, however, has not been scientifically validated for safety and efficacy. The aim of this study was to investigate antidiarrheal and antisecretory effects of hydroalcolic leaf extract of Z. scabra in mice models. Methods For each of antidiarrheal, gastrointestinal motility and antisecretory activity study Swiss albino mice were divided in to five groups. Group I was treated as control group and received 10 ml/kg of 2% Tween-80 orally; Group II served as a positive control and took standard drug in each of the experiments orally; Group III, IV and V were test groups which received the methanolic extract orally at 100, 200 and 400 mg/kg, respectively. Depending on the model total weight of fecal output, total weight of wet feces, total number of fecal output, number of wet faeces, length of intestinal transit and intestinal weight were collected. Finally, data were analyzed using one-way ANOVA followed by Tukey’s post test. Result In castor oil induced diarrhea model, the extract dose produced a significant reduction in mean stool score (1.94 ± 0.102) at 200 mg/kg. Moreover, the 100, 200, and 400 mg/kg doses inhibited stool frequency by 40, 45 and 55%, respectively. All test doses of extract and loperamide (3mg/kg) reduced fecal fluid content significantly (p
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