BACKGROUND Catha edulis Forsk. (Khat) is traditionally used for treating various disorders. Nevertheless there are no reports of any scientific assessment of its psychopharmacological properties. OBJECTIVE Therefore, the current study was designed to evaluate the antidepressant-like activity of Khat ethanolic extract using established animal models of depression and stress. METHODS Ninety healthy male albino mice were used in this study. Forced swim, tail suspension and head poking tests were utilized to evaluate the antidepressant-like activity of the ethanolic extract of Khat (100, 200 and 400 mg/kg, i.p.) and escitalopram (standard drug) which were administered 30 min prior to the tests. Phytochemical analysis of the standardized extract was conducted using liquid chromatography-mass spectroscopy (LC-MS). RESULTS A significant decrease in the head-dipping behavior was noticed after administration of 100, 200 and 400 mg/kg of Khat extract. Moreover, the extract significantly decreased the immobility time in tail suspension and forced swim tests. The presence of cathinone and cathine were detected in the extract using LC-MS. CONCLUSIONS The current results suggest that the extract of Khat leaves has acute antidepressant properties and may have sedative effects. CONCLUSIONS Antidepressant-like activity of Khat established in vivoThe extract decreased the immobility time in tail suspension and forced swim testsLiquid chromatography-mass spectroscopy data revealed the presence of cathinone and cathine in Khat extract. Abbreviations used: LC-MS: Liquid chromatography-mass spectroscopy; NIST: National institute of standard technology; SSRI: Serotonin reuptake inhibitors; FST: Forced swim test; TST: Tail suspension test.