Introduction: Ziziphora tenuior L. (Z. tenuior) has multiple biological activities such as spasmolytic, antidiarrheal, analgesic, antidepressant and sedative effects. In the present study, the effect of ethanolic extract of Z. tenuior on morphine withdrawal symptoms was investigated in the male mice.Materials and Methods: In this study, 40 male mice weighing 20-30 g were used. The animals were divided into five groups of eight. The study groups included negative control or normal saline (10 ml/kg), positive control or clonidine (3.5 mg/kg), and different doses of Z. tenuior (50, 75, and 100 mg/kg). Dependency on morphine was induced by administration of different doses of morphine (50, 50, 75, and 50 mg/kg) in four days. On last day, after administration of single dose of morphine, naloxone (5 mg /kg) was injected and morphine withdrawal signs were observed and recorded within 30 min. All drugs and extracts were injected intraperitoneally with a single volume of 10 ml/kg.Results: Results showed that at all doses (50, 75 and 100 mg/kg) of Z. tenuior extract, significantly decreased the number of jumping (P<0.05, P<0.01 and P<0.001, for each concentration respectively) compared to control group. Teeth chattering and diarrhea decreased only with 75 and 100 mg/kg doses of extract (P<0.05). Rearing (P<0.05), climbing (P<0.05), writing (P<0.05), wet dog shakes (P<0.05) and grooming (P<0.01) behaviors decreased with all three doses of extract (P<0.05). In addition, clonidine as a reference drug significantly decreased all signs of withdrawal (P<0.05).Conclusion: Our results showed that ethanolic extract of Z. tenuior could alleviate morphine withdrawal signs. However, to determine the exact mechanism of action for Z. tenuior, the components have to be isolated and studied individually.