Euphorbia hirta L. (Euphorbiaceae) (E. hirta) is a tree locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, respiratory ailments, tumors, wounds, antipyretic, anti-inflammatory activities, etc. Therefore, we undertook to investigate their immunomodulatory effect on T lymphocytes (CD3+, CD4+ and CD8+ receptors) and Th1 cytokines (IL-2, TNF-α, IFN-γ) in a dose-dependent manner. E. hirta ethanol extract at 25, 50, 100 and 200 mg/kg doses was given orally for 7 days from the day of immunization. E. hirta maximum inhibition at 100 and 200 mg/kg p.o. was found to significantly block the production of the cell-mediated immune response, (CD3+, CD4+ and CD8+ receptors) and (IL-2, TNF-α, IFN-γ) and also prolongs graft rejection. E. hirta also showed a decrease of delayed hypersensitivity (DTH) response and dose-related decrease in the primary antibody response, respectively. Based on the data, it can be suggested that E. hirta is a potent and non-toxic immunosuppressor, which can be further explored for the development of potent immunosuppressor.