Chronic cerebral ischemia gradually generates cognitive impairment associated with modifications in the hippocampus, a brain structure that is largely involved in learning and memory processes. Such alterations have been attributed to the damage of neuronal plasticity of hippocampus. Numerous of studies demonstrated that bone marrow stromal cells (BMSCs) transplantation improved neural function of animal models with neurological diseases, including chronic cerebral ischemia. The effects of BMSCs transplantation attributed to modulation the express of Brain-derived neurotrophic factor(BDNF) and P75 neurotrophin receptor (P75NTR) are uncertain. To investigate the potential mechanisms of BMSCs transplantation for treating chronic cerebral ischemia, we established animal model by permanent occlusion of bilateral common carotid arteries and administrated BMSCs with green fluorescent protein (GFP) via tail vein at 48 hours after surgery. We found that the deficiency of spatial learning and memory caused by chronic cerebral ischemia were improved compared with vehicle-injected group. Meanwhile, results of immunohistochemistry in the CA1 region of hippocampus showed that the expression of BDNF was up-regulated and P75NTR was down-regulated. Our research suggested that BDNF and P75NTR could be influenced by BMSCs transplantation which is associated with the spatial learning and memory improvement. [Zhang HL, Song B, Gong GM, Wang YL, Qin J, Yang YK, Qi J, Chandra A, Xu YM. Bone marrow stromal cells transplantation impact spatial learning and memory and the expression of BDNF and P75NTR in rats with chronic cerebral ischemia. Life Sci J 2012;9(4):5936-5942] (ISSN:1097-8135). http://www.lifesciencesite.com. 890