Most of the synthetic chemotherapeutic agents used today are immunosuppressant and lead to numerous side effects. Plant based immunomodulators are employed as supportive therapy to counteract the undesirable side effects of chemotherapy. In the present study, the immunomodulatory and chemoprotective effect of methanolic extract of Acacia nilotica was investigated in mice. Intraperitoneal administration of the extract was found to significantly increase the Total WBC count, bone marrow cellularity and alpha-esterase positive cells. Cyclophosphamide is a chemotherapeutic drug and induces acute myelosuppression but treatment with the extract was beneficial in ameliorating chemically induced toxicity. The administration of the extract considerably increased the Total WBC count (6800 +/- 733.9 cells/cm2), bone marrow cellularity (43.6 x 10(5) +/- 14.33 cells/femur) and alpha-esterase positive cells (808.6 +/- 8.57 cells/4000 cells) in CTX treated mice when compared to CTX alone treated control mice. Weight of lymphoid organs such as spleen and thymus reduced by CTX were enhanced by treatment with Acacia nilotica extract. It can be concluded that the extract possess immunostimulatory properties.