Abstract: OBJECTIVE To investigate the ameliorative effects of sepia ink polysaccharides (SIPS) on liver, kidney, heart and lung injuried by cyclophosphamide. METHODS BALB/c mice were orally administered with SIPS (180 mg·kg^-1) for two weeks, once a day, and given intraperitoneal injection of cyclophosphamide (100 mg·kg^-1) on the 6th and 7th day during experimental of 14 days. Organ indexes and antioxidant abilities of liver, kidney, lung and heart, as well as functions of liver and kidney were detected. RESULTS SIPS not only significantly impaired the increase of liver index (P<0.01), GPT and GOT activities (P<0.01) and decrease of serum BUN (P<0.01), also obviously protected antioxidant ability of liver (P<0.01) and heart (P<0.05). CONCLUSION The data indicates SIPS alleviate toxicity of CP on the four organs induced by cyclophosphamide.