To study the antidepressant effect and mechanism of the essential oil (EO) from Pelargonium graveolens and Ocimum basilicum L..In this study,the model of “behavioral despair and depression” was established by using mouse tail suspension test (TST) and forced swimming test (FST),and then the immobility time of the model mice was measured.PC12 cells were injured by corticosterone (CORT) to establish stress injury model,and MTT assay was used to detect cell viability.The antidepressant effect and mechanism of EO from P. graveolens and O. basilicum were studied.The results showed that in the two “behavioral despair and depression” model tests,compared with the normal control group,each experimental dose group (0.24,0.36,0.48 mL/kg) of the two EO could effectively shorten the immobility time of depression model mice.However,in CORT stress injury cell model test,the cell survival rate of the model group decreased obviously,and the cell synapses contracted.When two kinds of EO were given,the cell survival rate was significantly improved,and the synapses were recovered.In addition,it was found that PI3K/Akt and PKA signal pathway inhibitor could significantly reduce the protective effect of geranium and basil essential oil against corticosterone.The above results indicated that EO have certain antidepressant effects,and their neuroprotective effects may be mediated by PI3K/Akt and PKA signaling pathways.