Studies have reported that plant extracts possess medicinal values including immunomodulatory activities. This study was carried out to evaluate the immunomodulatory effect of different concentrations of aqueous extracts of Telfairia occidentalis in male wistar albino rats. The extract was administered orally by gavage at doses of 100mg/kg and 300mg/kg daily to immune depressed rats divided into 4 groups for 21days. The assessment of immunomodulatory effect of this plant was carried out by testing the changes in the humoral and cellular immune responses of the animals challenged by sheep red blood cells (SRBCs). The results obtained showed a significant (p < 0.05) increase in the TWBC at 300mg/kg dose and no significant difference (p > 0.05) at the 100mg/kg dose when compared to the control. The PCV test showed a significant (p < 0.05) increase at both doses (100mg/kg and 300mg/kg). The RBC count showed a significant (p < 0.05) increase at the 300mg/kg dose while there was no significant difference at the 100mg/kg dose. The DTH response also showed a significant increase at both doses compared to the control. The plant extract equally showed elevated humoral antibody response at dose of 100mg/kg and 300mg/kg and this was significant. In all, Telfairia occidentalis exhibited an immunostimulatory effect on the humoral immune function and anti-inflammatory activity on the cell mediated immune response in wistar albino rats.