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To investigate the effects of paroxetine on the cell viability and expression of the phosphorylated ERK1/2 in LPS injured hippocampal-derived neural stem cells (NSCs).The NSCs were derived from hippocampus of fetal rats, after the primary neurospheres passaged,the cells were treated with LPS (200 ng/ml) and different concentrations of paroxetine for 72 h.Then the cell viability and the protein level of pERK1/2 were measured by the kit of WST-8 and westem blot, respectively.Furthermore, after treated with U0126, the apoptosis rate was measured by using Annexin-V-FLUOS Staining Kit.The cell viability in 5 μM paroxetine treated group was higher than LPS group (P < 0.01), but there were no significant differences between other paroxetine treated groups and LPS group.When detected by western blot, the expression of pERK1/2 in paroxetine 5 μM treated groups or sham group was significant higher than LPS group, respectively (P < 0.01).Furthermore, coincide with cell viability, the apoptosis of 5 μM treated groups or sham group was significant lower than LPS group by using flow cytometry;U0126 promoted the apoptosis of LPS treated groups,and there was no significant difference between paroxetine + LPS treated groups and LPS group.The cellular damage of NSCs injured by LPS can be restrained by paroxetine, which were possibly carried out by affecting ERK1/2 pathway.