BACKGROUND The objective of this study was to explore the immunomodulatory effect of khat and its active component, cathinone, using mice. METHODS Female Swiss albino mice aged 7-8 weeks weighing 25-30 g were used in the study. Mice were randomized into eight groups of 6 each and oral treatment of khat crude extract and cathinone were given daily for four weeks. Physical, hematological, biochemical, and immunological parameters were measured. Immunological studies included humeral immunity (IgG and IgM), cellular immune response (delay type hypersensitivity), phagocytic activities of reticuloendothelial system, and determination of T-lymphocyte population: CD3(+), CD4(+), CD8(+) count and CD4(+)/CD8(+) status. RESULTS Findings of this study showed that, khat and its major metabolite, cathinone, can positively affect immune system in dose dependent manner. When doses of crude khat extract and cathinone increase, the induction of humeral (IgG and IgM) and cellular immune responses were up-regulated significantly (P < 0.05), while at higher dose of khat (200 mg/kg) cellular immune response was suppressed. In support of this, as doses of the two test substances increased, the count of T helper cells (CD4(+)) was significantly increased (P < 0.05), while higher dose significantly reduced whole white blood cell (WBC), CD8(+), and CD3(+) counts. CONCLUSIONS At relatively lower dose (50-100 mg/kg), crude khat extract has immune stimulating property, although higher dose (200 mg/kg) leads to suppression of cellular immune response. Cathinone also share all immune modulating property of its parent compound, khat, but with intense strength. Thus, it calls for further detailed investigation of khat for practical application of the same in human medication.