Objective To observe the effects of Naokang II ,a traditional Chinese medicine on spatial learning and memory abilities and hippocampal neurogenesis in rats with cerebral ischemia. Methods A total of 54 SD rats were divided into 6 groups according to the digital random method: A control,a sham operation , a model, a low-dose,a medium-dose, and a high-dose Naokang II group ( the low-, medium-, and high-dose groups were 5,10, and 20 times of adults (n = 9 in each group). A rat model was induced by ligate the bilateral common carotid arteries permanently. The bilateral common carotid arteries were only isolated but not ligated in rats of the sham operation group. The rats in the control group were not given any treatment. After modeling, the rats in the treatment groups were treated with Naokang II . The rats in the control, sham operation, and model groups were given equal volume of isotonic saline (2ml). Morris water maze test and space search experiment were used to evaluate the learning and memory abilities in rats 9 weeks after modeling. Immunofluorescence staining and immunohistochemical methods were used to observe proliferation and differentiation of neural stem cells (NSCs). Western blot was used to detect the expression of autophagy related protein Beclin-1 and LC-3 II . Results ( 1 ) The escape latencies of the model group from 1 to 5 days were 100 ± 13,98 ± 13,82 ± 14,72 ± 15, and 46 ± 7 s, respectively. They were significantly longer than those of the sham operation group and the control group (all P <0.05). The search distances were 1239 ± 127,1011 ± 122,959 ± 123 ,553 ± 66, and 407 ± 29 cm, respectively. They were significantly increased as compared with those of the sham operation group and control group ( all P < 0.01 ). Both the escape latencies and search distances of the rats in the Naokang H low-, medium-, and high-dose groups were significantly shorter than those of the model group (P <0. 05). The escape latencies on the fifth day were 20 ± 6 ,19 ± 8 , and 15 ± 6 s, respectively, and the search distances were 234 ± 38 , 297 ±23, and 99 ±22 cm, respectively. Nine weeks after modeling, the quadrant search time on the original platform in the rats of the model group was 30 ± 9 s, it was significantly shorter than that of the sham operation group (P <0. 01 ). The quadrant search time on the original platform of the Naokang II low-, medium-, and high-dose groups were 34 ±6,38 ± 8 , and 40 ± 10 s , respectively. They were significantly longer than those of the model group ( P < 0. 01 ). (2) Nine weeks after modeling, the results of immunofluorescence and immunohistochemistry showed that the number of BrdU-positive cells and the Nestin positive cells in hippocampal dentate gyrus of the model group were higher than those of the control group and the sham operation group (P < 0. 05). The number of BrdU-positive cells and Nestin positive cells of Naokang H each dose group were significantly higher than those of the model group ( P < 0. 05 ) . The expression of LC-3 II and Beclin-1 in the model group was significantly higher than those in the control and sham operation groups (P < 0. 01). The expression of LC-3 II in the medium- And high-dose groups was 143 ±9 and 129 ± 9 respectively,and the expression of Beclin-1 was 139 ± 10 and 124 ±7 respectively, and they were significantly lower than the model group ( P < 0. 01). Conclusion Naokang H can improve the cognitive function in rats with cerebral ischemia,promote neurogenesis in the dentate gyrus,and inhibit autophagic cell death. Copyright © 2014 by the Chinese Medical Doctor Association.