Background: Promising results were obtained by using medicinal plants for the treatment and prevention of opioid withdrawal syndrome. A native Iranian plant, Echinophora platyloba, has shown analgesic effects that may be mediated through opioid receptors. Thus, the present research evaluated the effects of the ethanolic extract of E. platyloba on the acquisition of morphine dependence in mice. Methods: Thirty-two male mice were randomly allocated into four groups of eight. Morphine dependence was induced in the mice by subcutaneous administration of morphine (50, 50, and 75 mg/kg)×3 days, plus a single dose of morphine (50 mg/kg) on the fourth day. Withdrawal syndrome was precipitated by intraperitoneal injection of naloxone (4 mg/kg) 2 hours after the last dose of morphine. On days of dependence induction and before each morphine dose, the mice received intraperitoneal injections of saline (10 ml/kg) or plant extract (25, 50, and 75 mg/kg). After the injection of naloxone, the symptoms of withdrawal syndrome in each animal were monitored for 30 minutes. Results: Administering morphine with this method induced morphine dependence in mice that were treated with saline before morphine. However, the mice that received the plant extract showed a significant decrease in the withdrawal symptoms including the number of jumping (P<0.01), rearing (P<0.05), grooming (P<0.05), and diarrhea (P<0.01) compared with the saline-treated mice. Conclusion: Administration of the hydro-ethanolic extract of E. platyloba before morphine may inhibit the induction of morphine dependence. Therefore, the plant extract may be considered a therapeutic agent for the prevention of morphine dependence in morphine users.