Background: Ionizing radiation induces the production of reactive oxygen species (ROS), which play an important causative role in cell death. The aim of this study was to investigate the protective effects of sulfated derivatives of neutral polysaccharides extracted from Auricularia auricular (SNAAP). Materials and Methods: Whole blood samples from healthy donors treated with SNAAP at different concentrations (20, 60, 100 &mug/mL) were exposed to various doses of X-rays. Wistar rat spleen lymphocytes, in cultures, were treated with SNAAP at different concentrations (20, 60, 100 &mug/mL) in the presence p.o 12 hours prior to 8 Gy gamma radiation exposure. Animals were administered with SNAAP at doses of 50, 100 or 200 mg/kg body weight d p.o 7 days prior to sub-lethal doses (6 Gy) of whole body gamma radiation exposure. Results: SNAAP is an effective radio protector against X-ray radiation induced in vitro cellular damage in human peripheral blood. Furthermore, to support this finding the effect of SNAAP on a rat’s spleen lymphocytes, when cultured and examined 24 hours after exposure to 8 Gy &gamma of radiation, demonstrated the effect of polysaccharides on a rat’s spleen lymphocytes, pretreated by the SNAAP, can increase the cell viability compared with irradiated group at a concentration of 20, 60 and 100 &mug/mL. Likewise, this radiation-induced therapy decreased each mouse’s body weight and effectively stimulated the immune system of all radiated mice. Moreover, when induced by Co60, the SNAAP decreased the level of malondialdehyde (MDA) and increased the myeloperoxidase (MPO) and the glutathione peroxidase (GSH-Px) activity in the whole blood supply of the irradiated mice. Conclusion: These encouraging results support further research into the clinical pharmacology of SNAAP as a novel agent for human radiation protection.