Introduction: Cerebral ischemic stroke is the third cause of death worldwide and is one of the main causes of long-term disabilities. Histone deacetylase inhibitors have effects on amelioration of brain disorders. The purpose of this study was to investigate the effects of sodium butyrate (SB) as a histone deacetylase inhibitor on short-term working memory and serum level of B-cell lymphoma 2 (Bcl2) protein in a rat cerebral hypoxic ischemia (HI) model. Materials and Methods: The animals were divided into 5 groups; control, HI+Saline, HI+SB 0.1, HI+SB 0.3, and HI+SB 0.6. Ischemia was induced by left carotid artery occlusion and then rats were placed in the hypoxic chamber containing 8% oxygen for 5 minute. SB was injected at doses of 0.1, 0.3 and 0.6 (mg/kg/day) intra-peritonealy for 14 consecutive days in three treatment groups. Short-term working memory in these groups was analyzed by Y-maze test. After performing the test, serum value of Bcl2 protein were measured by ELISA. Results: The percent of behavior alteration was higher in treatment groups than HI+Saline group in a dose dependent manner. In addition, SB administration reduced serum levels of Bcl2 in treatment groups. Conclusion: SB may cause amelioration of short-term memory and reduction of Bcl2 level, as an apoptosis marker, in cerebral hypoxic ischemia.