Jujuhoside A (JUA) is a main component of jujubogenia exrracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traitional metiicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitinry effects of JuA on hippocampal forma-tion in vivo and in vitro, the present study was carried out to ex amine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocamput. Microdialysis coupled with high-performance Liquid chromatography (HPLC) was used to monitor the changes of Glu Levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal GlU concentration (p<0.Ol) and a high dose of JuA (0.1g/L) sig-mificantly blocked penicillin-indued Glu release (P<0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with can focal laser scanning microscope (CLSM). It was found that Clu (O.5 mM) reduced an intracellular [Ca2+], increase (p<0.01), and JuA significantly inhibited the Glu-induced Ca2+. increase. The calmodulin (CAM) antatgonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested tbat JuA has inhibitory effects on Glu-mediated excita-tory signal pathway in hippocampus and probably acts through its anti-calmodulin action