Our previous studies demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibit potent immunomodulating effects. Immunomodulation plays an important role in hematopoiesis. To investigate the possible mechanism by which Gl-PS promote myelopoiesis during myelosuppression induced by cyclophosphamide, mice were injected intraperitoneally (i.p.) once daily with 2.5 mg/kg of Gl-PS for 10 days and were treated i.p. once daily with cyclophosphamide (100 mg/kg) on days 2 through 4. In the present study in vivo and in vitro, we find that Gl-PS selectively bind to bone marrow stromal cells, stimulate the secretion of hematopoietic growth factors, and enhance the clonogenic activities of hematopoietic and stromal cells to promote hematopoiesis in myelosuppressed mice