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Objective To observe pancreatic ER kinase(PERK) signaling of unfolded protein response(UPR). Methods The rats were divided into control, model, and ginsenoside Rb1(Rb1) groups, and put into hypoxia chamber to establish the acute plateau stress model. The water solutions of Rb1 were given to rats in Rb1 group for 7 d. After that, The behavior of rats was observed by Y-maze and passive avoidance test and the rats were sacrificed in a batch for detection by Western blotting. Results Hypobaric hypoxia mediated UPR pathway accompanied the activation of protective pathways such as PERK-e IF2a-ATF4 and Grp78/Bip pathways. On the other hand, Rb1, the extract from herbal medicine ginseng, increased on the expression of PERK, e IF2 a, ATF4, and Grp78/Bip in rats. Conclusion The results indicate that PERK-e IF2a-ATF4-GRP78 pathway is a potential target for therapeutic applications in high altitude diseases and Rb1 can attenuate the injury to memory function caused by hypobaric hypoxia neurotoxicity.