Aim： To investigate the effect and underlying mechanisms of polygalasaponin F （PGSF）, a triterpenoid saponin isolated from Polygala japonica, on long-term potentiation （LTP） in hippocampus dentate gyrus （DG） of anesthetized rats. Methods： Population spike （PS） of hippocampal DG was recorded in anesthetized male Wistar rats. PGSF, the NMDAR inhibitor MK801 and the CaMKII inhibitor KN93 were intracerebroventricularly administered. Western blotting analysis was used to examine the phosphorylation expressions of NMDA receptor subunit 2B （NR2B）, Ca^2＋/calmodulin-dependent kinase II （CaMKII）, extraceilular signal- regulated kinase （ERK）, and cAMP response element-binding protein （CREB）. Results： Intracerebroventricular administration of PGSF （1 and 10 μmol/L） produced long-lasting increase of PS amplitude in hippocampal DG in a dose-dependent manner. Pre-injection of MKS01 （100 μmol/L） or KN93 （100 μmol/L） completely blocked PGSF- induced LTP. Furthermore, the phosphorylation of NR2B, CaMKII, ERK, and CREB in hippocampus was significantly increased 5-60 min after LTP induction. The up-regulation of p-CaMKII expression could be completely abolished by pre-injection of MK801. The upregulation of p-ERK and p-CREB expressions could be partially blocked by pre-injection of KN93. Conclusion： PGSF could induce LTP in hippocampal DG in anesthetized rats via NMDAR activation mediated by CaMKII, ERK and CREB signaling pathway.