Ｏｂｊｅｃｔｉｖｅ　To observe the effects of histone deacetylase（HDAC） inhibitor sodium butyrate（NaB） on sevoflurane-induced long-term cognitive dysfunction in neonatal rats.　Methods　Twenty-four male Sprague-Dawley（SD） rats at postnatal day 6 were randomly divided into the following three groups（n=8） in accordance with a random number table： O2+normal saline group （O2+NS group）， sevoflurane anesthesia+normal saline group（Sev+NS group） and sevoflurane anesthesia+sodium butyrate group（Sev+NaB group）. Animals were subjected to 3% sevoflurane plus 100% O2 or 100% O2 2 h daily for 3 consecutive days， respectively. Thereafter， animals in different groups were chronically given intraperitoneal injections of NS（10 ml/kg） or NaB （1.2 g/kg） for 32 d， respectively. Open field was performed at postnatal day 31， and the Morris Water Maze test was performed at postnatal day 34-40. The hippocampus was harvested 1 h after the behavioral test to measure the content of HDAC2， brain-derived neurotrophic factor（BDNF）， postsynaptic density 95（PSD95） and microtubule associated protein（MAP2）. Immunofluorescence was used to confirm the fluorescence intensity of acetyl-histone H3 lysine 9（H3K9） and acetyl-histone H4 lysine 12（H4K12） in the hippocampus subfields.　Results　In the open field test， there was no significant difference in the total travel distance， speed， and the time spent in the center of the arena among the three groups（P>0.05）. In the Morris Water Maze test， the escape latency at postnatal day 36-37 increased significantly， the time spent in the target quadrant［O2+NS group：（30.2±2.8） s， Sev+NS group：（16.8±2.9） s， Sev+NaB group：（28.3±3.4） s］ and times across the original platform［O2+NS group：（5.4±0.8） times， Sev+NS group：（2.5±0.8） times， Sev+NaB group：（5.5±0.7） times］ reduced significantly， the content of HDAC2 increased significantly， fluorescence intensity of acetyl-H3K9 and H4K12 in hippocampal CA1 region and the content of BDNF， PSD95 as well as MAP2 decreased significantly in the Sev+NS group compared with the O2+NS group（P<0.05）. However， NaB by intraperitoneal injection could reverse the above measurement indicators to normal levels（P<0.05）.　Conclusions　Histone deacetylase inhibitor NaB can alleviate sevoflurane anesthesia-induced hippocampus-dependent long-term cognitive dysfunction in neonatal rats， which is associated with the up-regulation of histone acetylation and synaptic plasticity in hippocampus.