Mitragyna Speciosa Korth (MS) was used as an opium substitute in Southeast Asia. It has been shown to have addictive properties and to produce tolerance and dependence. The methanolic leaf extract of Mitragyna Speciosais Known to contain several alkaloids including mitragynine which structurally has an indole moiety. This moiety is also a feature of serotonin which is an important neurotransmitter in depression. This would tend to suggest some activities of MS at the brain serotonergic system. On the other hand, current strategy in designing antidepressants in the form of selective serotonin reuptake inhibitors (SSRIs), this study has investigated whether the methanolic leaf extract of MS possesses antidepressant-like effect. The Porsolt swim test method (PST) for screening antidepressants had been used. Female mice were forced to swim for 6 minutes. This was followed 24h later with a second swim session of 6 min. Drugs were administered (n=10) orally1, 5 and 24h after the first swim session to record chronic effect. The oral administration of MS methanolic leaf extract at doses 100, 200, 400 mg/kg, significantly reduced the immobility time.