The present study was designed to determine in vivo efficacy of Ganoderma lucidum polysaccharides (Gl-PS) for enhancing the activity of immunological effector cells in immunosuppressed mice. Mice were injected intraperitoneally (i.p.) once daily with low-dose (2.5mg/kg), intermediate-dose (25mg/kg), and high-dose (250 mg/kg) of Gl-PS, respectively, for 7 consecutive days 24h after i.p. injection of a immunosuppressing anti-tumor agent cyclophosphamide (Cy, 300 mg/kg). In Cy-treated mice, compared to vehicle, low-dose Gl-PS accelerated recovery of bone marrow cells, red blood cells and white blood cells, as well as splenic natural killer cells and natural killer T cells, and enhanced T and B cell proliferation responses on day 8, cytotoxic T lymphocyte activity on day 5, as well as NK cell and lymphokine activated killer cell activity on days 7-9. Furthermore, it promoted phagocytosis and cytotoxicity of macrophages on day 12. The above beneficial effects induced by the low-dose Gl-PS treatment did not result in any side effects. These results demonstrate the efficacious effects of low-dose Gl-PS treatment for enhancing the activity of immunological effector cells in immunosuppressed mice, and may provide a basis for applying this herb as an efficacious adjacent immunopotentiating therapy against cancer chemotherapy-induced immunosuppression.