Morphine, when administered in high doses, can increase locomotor activity in laboratory animals. The role of dopaminergic, GABAergic, and opioid systems of the brain in modulating locomotor activity caused by morphine is well-defined. The extract of Khosharizeh has alkaloid and terpene compounds that are known to be effective on the opioid and GABAergic systems of the brain. Thus, this study aimed to investigate the possible effects of the hydro-alcoholic extract of Khosharizeh on the increase in locomotor activity caused by morphine. In this study, 112 male mice with an average weight of 24-28 grams were used. The mice were randomly divided into 14 groups. Then, they were treated with Khosharizeh extract (25, 50, and 75 mg/kg, intraperitoneally) or morphine (1, 5, 10, and 20 mg/kg, subcutaneous). Control groups received saline. In the final part of the experiment, the remaining four groups, one hour before the administration of the morphine (40 mg/kg), received Khosharizeh extract or saline. A high dose of morphine (40 mg/kg) significantly increased the locomotor activity of mice. Also, the administration of Khosharizeh extract alone caused a decrease in motor activity in all doses. Finally, the administration of Khosharizeh extract before morphine significantly inhibited the increase in locomotor activity induced by morphine. Probably, the extract of Khosharizeh can interfere with the locomotorstimulating effects of morphine through the opioid and GABAergic systems of the brain.