The present study was conducted to investigate the preventive effects of squid ink polysaccharides (SIP) on the damage of sperm and reproduction induced by cyclophosphamide that is most commonly used for treating clinically cancers. Male Kunming mice exposed to cyclophosphamide were administered with SIP and were sacrificed to determine sperm parameters, testicular antioxidant ability and reproductive capacity. Data indicated that cyclophosphamide caused obvious changes in mice such as significant reduction (P<0.01) of glutathione reductase activity (GR), vitamin C (Vc) content and total antioxidant capacity (T-AOC) in the testes, as well as elevation (P<0.01) of abnormal rates of sperm and fetus, and a decrease in the total fetal count and average fetal count (P<0.01), were totally alleviated by SIP. From these findings it can be concluded that SIP decreases chemotherapeutic damage to sperm and reproduction in mice induced by cyclophosphamide.