Objective:To investigate the improvement of radiation-induced cognitive dysfunction and its preliminary mechanism by Ilex pubescens var.kwangsiensis.Methods:SPF grade male Kunming mice were randomly divided into control group(Control),Ilex pubescens var.kwangsiensis(IP),radiation group(Rad)and radiation+Ilex pubescens var.kwangsiensiss group(Rad+IP),with 10 mice in each group.Morris water maze test and dark avoidance test were used to detect the changes in cognitive function of mice before and after drug intervention.Hematoxylin-eosin(HE)staining and electron microscopy were used to observe the changes of brain histopathology and ultrastructure in the hip-pocampus of mice.The expressions of nuclear factor E2-associated factor 2(Nrf2),heme oxygenase 1(HO-1),man-ganese superoxide dismutase(MnSOD),B-cell lymphoma/leukemia-2(Bcl-2)and Bcl-2 associated X protein(Bax)were detected by immunohistochemical assay.Results:The expressions of MnSOD and Bcl-2 in hippocampal tissue of mice in Rad group were significantly decreased,the expressions of Nrf2,Bax and HO-1 were significantly increased,and the nuclear translocation of Nrf2 was also significantly increased.After intervention,he expressions of MnSOD,Nrf2 and HO-1 were significantly increased,and the apoptosis rate was significantly decreased.Conclusion:Ilex pu-bescens var.kwangsiensis improved cognitive dysfunction in mice after radiation,and the mechanism may be related to Nrf2 activation and regulation of HO-1 transcription and expression,reducing oxidative stress damage.