Abstract: Post-Stroke Depression (PSD) always leads to various cognitive deficits and many unfavorable outcomes. The aim of this study was to examine the protective effects of Wuling capsule on changes of hippocampal-dependent learning and memory and expression of Brain-Derived Neurotrophic Factor (BDNF) in hippocampus. Adult male Sprague-Dawley rats were exposed to a 3-week chronic mild stress paradigm after ischemic surgery. The level of depression was assessed with sucrose preference and the morris water maze was introduced to detect the changes of learning and memory. The BDNF expression was examined by immunohistochemical staining and the assay of mRNA amplification using semi-quantitative reverse transcription-PCR. A significant decrease in the sucrose preference and BDNF expression was found in the model rats. Escitalopram was administrated orally at a dose of 0.2 mg kg -1 b.wt. day for 21 days. The depressed behavior was improved and the cognitive deficits recovered to normal level. Moreover, the low expression of BNDF increased significantly. The same changes were found in Wuling capsule treatment at the dose of 100 mg kg -1 b.wt. except that BDNF expressions remain low after treatment. These results indicate that the mechanisms of Wuling capsule improving the impairments of learning and memory in PSD rats are not mediated by BDNF.