Abstract:A mouse model of radiation damage was established. The body weight growth curve，white blood cell count，organ indexes，and levels of interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）of mice were analyzed. The immune organs were stained with hematoxylin-eosin（HE）. The expression levels of Tolllike receptor 4（TLR4）and nuclear factor kappa-B（NF-κB）P65 in the spleen tissue were determined to study the mechanism of Stropharia rugosoannulata polysaccharide in alleviating radiation damage in mice.The results showed that S. rugosoannulata polysaccharide not only effectively increased the peripheral white blood cell count and organ indexes but also effectively inhibited the secretion of inflammatory factors，reduced the damage of the spleen，thymus，liver，and colon tissue，and down-regulated the mRNA and protein levels of TLR4 and NF-κB P65 in the spleen tissue. In summary，S. rugosoannulata polysaccharide effectively alleviated the organ damage caused by radiation and inhibited the inflammatory responses caused by radiation by acting on the TLR4/NF-κB pathway in mice.It demonstrated potential as a protective agent for radiation damage.