Objective To investigate the effect of active factor on proliferation and differentiation of neural stem cells (NSCs) in the hippocampal subgranular zone after traumatic brain injury (TBI) in rats.Methods SD rats were divided into sham-injured group (only left dura mater exposed),active factor group (sham injury + active factor therapy),TBI group (unilateral fluid percussion was used to generate severe TBI),and TBI + active factor group (TBI + active factor therapy) according to the random number table (n =10 in each group).Hippocampal homogenates or brain tissues were harvested at 7 d postinjury.Expressions of BrdU and NeuN in the hippocampal subgranular zone were detected by immunofluorescence staining,and five consecutive sections were used to count BrdU and NeuN positive cells.Level of nuclear factor (NF)-κB p65 in hippocampus was detected by Western blot.Results Number of BrdU and NeuN positive cells in TBI group were greatly higher than that in sham-injured group (P ＜ 0.05).Number of BrdU and NeuN positive cells in TBI + active factor group was greatly higher than that in TBI group [(207.7 ±22.5) vs.(115.9 ± 13.3)] (P ＜0.05).There were no significant differences in BrdU and NeuN positive cells between sham-injured group and active factor group (P ＞ 0.05).NF-κBp65 presented over-expression in TBI group (0.81 ±0.09) while reversed in TBI + active factor group (1.46 ±0.13),when compared to sham-injured group (P ＜ 0.05).However,no significant change in NF-κBp65 was noted between sham-injured group and active factor group (P ＞0.05).Conclusion Active factor therapy can promote proliferation and neuronal differentiation of NSCs in the hippocampal subgranular zone after TBI in rats and the possible mechanism may relate to activation of the NSCs and inhibition of over-expression of NF-κBp65.