Objective To explore the molecular mechanism of hippocampal histone deacetylase （HDACs） related to the decline of brain learning and memory caused by repeated mild traumatic brain injury （rMTBI）. Methods The changes of hippocampal HDAC activity and learning and memory ability at 48 hours and 4 weeks after rMTBI in rats were analyzed using the rat rMTBI model and new thing recognition detection. We used tricostatin A （TSA）， a pan HDAC inhibitor， to observe the effect of TSA on HDAC activity and learning and memory ability. Results rMTBI increased the mRNA levels of different subtypes of HDAC 2-5 and HDAC 11 at different time points， with the increase of the activity of HDAC in nucleus and cytoplasm. However， compared with the Sham group （1.02±0.14）， the mRNA level of HDAC8 decreased significantly to （0.47±0.09） 4 weeks after injury （t=8.095，P ＜ 0.001）. After treatment with TSA， the learning and memory deficit and HDAC activity caused by rmtbi returned to normal. Conclusions rMTBI may up-regulate the activity of some HDAC subtypes， resulting in impaired learning and memory ability， while HDAC activity inhibitors have potential in the treatment of cognitive defects caused by rMTB.