OBJECTIVE：To study the protection ef fects of mulberry anthocyanin- 3-glucoside on epilepsy model mice and the effect of hippocampal brain derived neurotrophic factor （BDNF）/tyrosine kinase B （TrkB）pathway. METHODS ：Totally 120 C57BL/6 mice were randomly divided into normal group ，model group ，single medication group （mulberry anthocyanin- 3- glucoside），agonist combination group（mulberry anthocyanin- 3-glucoside+TrkB agonist LM 22B-10），with 30 mice in each group. single medication group and agonist combination group were given mulberry anthocyanin- 3-glucoside 600 μg/kg intragastrically once a day ，for consecutive 6 weeks. The agonist combination group was given LM22B-10（5 mg/kg）via the lateral ventricle once a day at 6th week. Normal group and model group were given constant volume of normal saline intragastrically. After last medication，except for normal group ，other groups were given lithium chloride-pilocarpine to establish epilepsy model. After modeling，10 mice in each group were taken to record the latency ，frequency and duration of spontaneous recurrent epilepsy ， observed for 6 hours a day for 4 weeks；EEG was recorded on the 14th，28th and 36th day after modeling ，and the abnormal frequency of EEG in 1 h was counted . On the 6th day of modeling ，other 10 mice in each group were taken to detect the serum calcium level ，and the remaining 10 mice in each group were taken to detect the expressions of BDNF mRNA and protein in the hippocampus. RESULTS ：Compared with normal group ，latency，frequency and duration of spontaneous recurrent epilepsy and the times of abnormal brain wave on the 14th，28th and 36th day after modeling were increased significantly in model group （P＜ 0.05）. The serum calcium level ， mRNA and proteinexpression of BDNF in hippocampus were increased E-mail：wangfang7699@126.com significantly （P＜0.05）. Compared with model group ，the latency，frequency，duration of spontaneous recurrent epilepsy and the times of abnormal brain wave on the 28th and 36th day after modeling were decreased significantly in single medication group（P＜0.05），while serum calcium level ，mRNA and protein expression of BDNF in hippocampus were decreased significantly （P＜0.05）. Compared with single medication group ，the latency，frequency and duration of spontaneous recurrent epilepsy and the times of abnormal brain wave on the 28th and 36th day after modeling were increased significantly in agonist combination group （P＜0.05），while serum calcium level ，mRNA and protein expressions of BDNF in hippocampus were increased significantly （P＜0.05）. CONCLUSIONS ：Mulberry anthocyanin- 3- glucoside has a good protection effect on epilepsy model mice ，the mechanism of which may be associated with inhibiting the activation of hippocampal BDNF/TrkB pathway.