Abstract: Objective: To explore the protective effect and mechanism of Ilex pubescens Hook.et Arn.(IPH) in radiation brain injury.Methods: Forty SPF Kunming mice were randomly divided into control group, IPH group, radiation group, and radiation+IPH group, with 10 mice in each group.The model of radiation brain injury was established by γ-rays, and the mice were given intragastric administration for 14 d before and after radiation.Morris water maze test and dark avoidance test were used to detect the cognitive function of mice.Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological changes of brain tissue, the ultra-electron microscope was used to observe the changes of glial cells, enzyme-linked immunosorbent assay (ELISA)was used to detect the serum level of interleukin-6 (IL-6), immunohistochemical method was used to detect the protein expression of c-Jun amino-terminal kinase(JNK), phosphorylated JNK(p-JNK), activator protein-1(AP-1), monocyte chemoattractant protein-1(MCP-1)in brain tissue, immunofluorescence was used to detect the protein expression of astrocyte marker GFAP and microglia marker Iba-1 in brain tissue, and western blotting was used to detect the protein expression of JNK and p-JNK in brain tissue.Results: Compared with the control group, the weight of the mice in the radiation group was reduced, and the serum IL-6 content, the expression levels of AP-1, MCP-1 and p-JNK/JNK ratio, as well as the expression levels of Iba-1 and GFAP in the microglia were increased 7 d after radiation(all P< 0.05).Compared with the radiation group, the weight of the mice in the radiation+IPH group was increased, and the serum IL-6 content, the expression levels of AP-1 and MCP-1 in brain tissue and p-JNK/JNK ratio, as well as the expression levels of Iba-1 and GFAP in microglia were decreased 7 d after radiation (all P< 0.05).HE staining and Nissl staining showed that a large number of cells and neurons in the radiation group appeared karyopyknosis, and microglia were activated and round; under the electron microscope, increased lysosomes were observed, with swelling of the nucleus and cytoplasm of astrocytes; after IPH intervention, the degeneration of neurons and the morphology of glial cells in the brain tissue of mice were significantly improved.Conclusion: Guangxi IPH can improve the cognitive function of mice with radiation brain injury and reduce the activation of microglia and astrocytes.The mechanism may be related to reducing neuroinflammatory response and inhibiting JNK/AP-1 signaling pathway.