In the present study, the effects of Pleurotus nebrodensis polysaccharide(PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide(40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M(Ig M) and immunoglobulin G(Ig G) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interferon-γ(INF-γ), and nitric oxide(NOS) in splenocytes. q RT-PCR results also indicated that PN-S increased the m RNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase(i NOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg / kg / 2d, CY) through intraperitoneal (PN-S) on the immune functions of immunosuppressed mice injection. The results showed that PN-S administration found radicalized by CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and additionally the immunoglobulin M (Ig M) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 TNF-α, IFN-γ, and nitric oxide (NOS) in splenocytes. Q RT-PCR results also indicated that PN-S increased the m RNA expression of IL-6, TNF-α, INF- These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.