OBJECTIVE： To study the effects of sodium butyrate on spatial learning and memory ability in chronic stress model rats. METHODS： SD rats were randomly divided into control group （normal saline）， model group （normal saline） and sodium butyrate low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg） with 14 rats in each group. Model group and sodium butyrate groups received plantar stimulation by electric shock for 21 d， once a day， 2 h each time， to induce chronic stress model.They were given relevant medicine ip 0.5 h before stimulation. Morris water maze test was adopted to test spatial learning and memory ability of rats （using escape latency as index， for consecutive 5 d）. Western blot assay was used to detect the expression of acH3， acH4， cAMP， p-CREB and BDNF in hippocampus. RESULTS： Compared with control group， escape latency of model group and sodium butyrate groups prolonged significantly on the second day （P＜0.05）， and the expression of acH3， acH4， p-CREB and BDNF decreased （P＜0.05）. Compared with model group， escape latency of sodium butyrate groups shortened， especially in high-dose group （there was statistical significance on the second day of test） （P＜0.05）； the expression of acH3， acH4， p-CREB， and BDNF enhanced （P＜0.05）. CONCLUSIONS： Sodium butyrate can improve chronic stress-induced the decrease of spatial learning and memory ability， the mechanism of which may be recovering histone acetylation level of chronic stress rat hippocampus， and increasing cognitive related proteins such as p-CREB and BDNF.