Introduction: Cerebral ischemia, occurs when a blood clot has occluded a brain artery, is the third leading cause of mortality in the Western world. The present study was aimed to investigate the effects of Trichostatin A (TSA), a histone deacetylase inhibitor, on cognitive deficits and serum Bcl-2 level in an animal model of hypoxia-ischemia rat model (HI). Materials and Methods: Thirty male Sprague dawley rats were randomly divided into the healthy control, HI+Saline and HI+TSA groups. The rats were suffered from the right common carotid artery ligation and 8% oxygen for 5 min to produce HI model. Two days after induction of ischemia, HI+TSA group received intraperitoneally TSA for 5 days. The Y maze test was used to assess the working memory. The ELISA test was performed to measure the serum Bcl-2 level. Results: The results showed amelioration of working memory in HI+TSA group compared to HI+Saline rats. In addition, a significant difference in the serum level of Bcl-2 was observed between HI+TSA and HI+Saline groups. Conclusion: The data suggested TSA as a potential treatment for amelioration of cognitive deficits after brain ischemia.