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To investigate the signal transduction of ginsenoside Rgl on ERK/MAPK pathway for understanding its effect on synaptic transmission.Methods: Electrophysiological recordings were conducted for basal synaptic transmission determination.Western blot were employed to examine the phosphorylation of ERK1/2, CaMK Ⅱ α and CREB.The confocal microscopy and fluorescent indicator Fluo-3 was applied to observe the intracellular calcium ion transcient change.Results: Rgl increased the population spike (PS) of hippocampal dentate gyrus.The phosphorylation of CaMKⅡ α, ERK1/2 and CREB in PC12 cells increased.The results of confocal microscopy observation showed that Rgl also promoted the transient enhancement of upstream calcium ion.Moreover, KN93, the inhibitor of CaMK Ⅱ α partially inhibited the activation of ERK1/2.The inhibitor of MEK PD98059 also partially blocked the phosphorylation of CREB.Conclusions: The CaMK Ⅱ α-ERK-CREB pathway might involve in potentiating synaptic transmission of Rgl, which may provide an explanation for the effect of Rgl on improving learning and memory.