Evodiae Fructus(EF) has been used as Traditional medicine for the treatment of headache, abdominal pain, hemorrhage, and menorrhae in many Asian countries. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunesuppression of water extracted EF(EFE). In the mouse spleen cell proliferation assay, EFE enhanced mitogenic activity and restored the CY-induced cell suppression. In the nitric oxide(NO) assay, EFE inhibited NO production and iNOS protein levels in LPS-stimulated RAW 264.7 cells. In the GC-MS analysis, many ingredients of EFE were detected by solvents. These results indicated that EFE can modulate immune response through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.