Objective To investigate the effect of Ginsensode Rgl on the expression of Neurogranin (Ng) and behavioral alteration in cortex and hippocampus of rats with chronic stress model.Methods A total of 36 adult male SD rats were randomly divided into control group (CON),model group (CUS) and treatment group (CUS-G).The chronic stress model was established by chronic unpredictable stress.The Morris water maze was used to study the learning and memory ability.The content of Ng in cortex,hippocampus was detected by RT-PCR and Western blot.Results The water maze test showed that after chronic stress,animal learning and memory ability decreased significantly,while the treatment group rats escape latency was significantly reduced (P＜0.05);after 6 weeks of stress,the cortex and hippocampus Ng mRNA levelschronic stress rats were markedly lower than that of model rats respectively (P＜0.05,P＜0.01,P＜0.05).The cerebral cortex and hippocampus Ng mRNA levels in treatment group were significantly increased compared with that of model group respectively (P＜0.01,P＜ 0.05,P＜0.05);The cerebral cortex and hippocampus Ng levels of chronic stress rat were significantly decreased when compared with that of the model rats respectively (P＜0.05,P＜0.01,P＜0.05),The cerebral cortex and hippocampus Ng content were significantly increased in treatment group compared with the model group respectively (P＜0.01,P＜0.05).Conclusions Chronic stress can change the behaviors of nice in recognization and memory The contents of Ng and the supplement of Ginsensode Rg1 have positive adjustment.