Aim: Many researches have shown that transplantation of bone marrow stromal cells (BMSCs) can reduce hypoxic-ischemic brain damage (HIBD), but the therapeutic window is unknown. This study is designed to conduct BMSCs transplantation on neonate rats following HIBD at different time points, and investigate the optimal therapeutic time window by assessment of long-lasting ethology and histology. Methods: This study was completed in the Central Laboratory of Xiangya Hospital of Central South University from June 2005 to June 2006. 1 Animals: Fifty 7-day-old SD rats of cleaning grade were divided into 5 groups at random: normal control group, model control group, 24-hour, 72-hour, 7-day transplantation groups (n=10). Another 10 4-week-old SD rats were prepared for culture of BMSCs. The rat treatments followed the animal ethics standard. 2 Experimental methods: Except the normal control group, the rats of other four groups were use to establish HIBD model. By means of stereotaxis instrument, 1 × 105 BMSCs (2 μ L) of passage 3 stained with Hochest33324 for 24 hours were transplanted into the left hippocampus at 24 hours, 72 hours and 7 day after induction of HIBD in the corresponding groups.3 Experimental assessment: Radial arm maze test was performed at 40 days, and the time taken to visit the 3 baited arms, number of error and number of repetition were recorded. After ethology test, Nissl staining of brain sections was used to count the neurons of CA1 area in the left hippocampus. The survival and proliferation of BMSCs were observed under fluorescence microscope, and immunofluorescence was used to identify the expressions of neuron specific encolase (NSE) of the transplanted BMSCs. Results: All of 50 rats were involved in the result analysis.1 Radial arm maze test: The time taken to visit the 3 baited arms, number of error and number of repetition in the model control group were higher than that of other groups (P < 0.01), and the rats of 24-hour transplantation group had lower results than those in the 72-hour and 7-day transplantation groups (P < 0.05). 2 Neurons of CA1 area in the left hippocampus in the model control group disordered and lost obviously, being significantly decreased compared with the normal control group (P < 0.01). The neurons arranged orderly in the transplantation groups, and were significantly increased compared with the model control group (P < 0.01). The neuron of CA1 in the left hippocampus of 24-hour transplantation group was more than that in the other two transplantation groups (P < 0.05).3 Proliferation and neural differentiation of the transplanted BMSCs: BMSCs survived and proliferated in the transplanted site and left cortex at 30-40 days after transplantation, and the NSE expression rate of BMSCs in the left hemisphere in the 24-hour transplantation group was remarkably higher than those in the 72-hour and 7-day transplantation groups (P < 0.01). Conclusion: Transplantation of BMSCs in neonate rats at 24 hours after HIBD has the maximal long-lasting ethological improvement, which is induced by brain damage, and the mechanism may be that early transplantation with BMSCs reduces effectively neuron necrosis and apoptosis, and is helpful for the migration and differentiation of BMSCs.