Objective To investigate the protective effect and mechanism of environmental enrichment(EE)on radiation induced cognitive dysfunction in mice.Methods A total of 45 female Kunming mice(2-month old)were randomly divided into control group,irradiation group and irradiation plus EE group with 15 in each group.Irradiation group and irradiation plus EE group were treated with a single dose of 4 Gy whole body irradiation,irradiation plus EE group were housed in EE condition for 35 d after irradiation.The object recognition task was used to evaluate the cognitive function of mice.The expression of microglial marker IBA-1 in hippocampus was determined by immunohistochemical staining.The expressions of CD68 and synaptophysin(SYP)proteins in hippocampus were assayed by Western blot.Results Compared with control group,the irradiation group had a low discrimination ratio in object recognition task and had a remarkable low level of SYP expression in hippocampus(t＝3.66,6.84,P＜0.05).In addition,radiation activated microglia in hippocampus by increasing the number of IBA-1-positive cells and enhancing the expression of CD 68(t ＝6.83,5.79,P ＜0.05).Compared with irradiation group,irradiation plus EE group increased the discrimination ratio and the expression of SYP in hippocampus(t＝3.56,4.06,P＜0.05),while the number of IBA-1-positive cells and the expression of CD68 were significantly reduced(t＝7.69,4.59,P＜0.05).Conclusions A single dose of 4 Gy whole body irradiation leads to cognitive dysfunction in mice,while EE could effectively improve the animals′cognitive behavior possibly by inhibiting microglial activation and preventing synapse loss in hippocampus.