Zingiberis rhizoma(ZB) has been used to treat a various condition and disease in many traditional preparation. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunotoxicity of aqueous-extracted ZB(ZBE) using in vitro and in vivo experiment. In vitro experiment, the mouse spleen cells proliferation and nitric oxide(NO) production in RAW 264.7 mouse macrophage cells were investigated. ZBE enhanced mitogenic activity in mouse spleen cells. The suppression of CY-induced mouse speen cell proliferation was significantly restored by ZBE treatment. ZBE inhibited NO production, iNOS mRNA and protein levels in LPS-stimulated RAW 264.7 cells. In vivo experiment, ZBE was orally administrated(single dose of 150mg/kg for 12 days) and CY i.p(150mg/kg) injected to SD rats. In CY alone injected group, body weights and spleen weights, and a various hematological parameters were reduced when compared with control group, whereas those values were increased by concomitant treatment of CY and ZBE when compared with CY alone injected group. These results indicated that ZBE can modulate CY-induced immune suppression through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.