Objective To investigate the proliferation and survival of endogenous new born cells in the hippocampus of post-stroke depression (PSD) rats. Methods Male SD rats were divided into 4 groups (n = 18): control, stroke, depression and PSD group. The animals were subjected to left middle cerebral artery occlusion (MCAO) reaulting in consistent focal cerebral infarcts, followed by an 18-day exposure to chronic mild stress (CMS) and single housing to induce PSD animal model The dynamic expression of brodmodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) in the left dentate gyrus of hippocampus were determined by immunohistochemistry or double-lable immunofluorescence staining. BrdU was a marker of new born cell, NeuN and GFAP marked that new born cell differentiated into neuron and astrocyto respectively. Results Compared with ischemia animals (232.2±8.6,123.7±2.6,136.2±2.6), in the left dentate gyrus, PSD samples had significantly less BrdU-positive cells ( 156.2±2.5, t =28.83, P < 0.01 ) on the 21st day after ischemia, and on day 30 and 45 ( 70.2±2.0, 81.2±1.1, t = 52.27, 62.08, both P < 0.01 ). The ratio of BrdU-positive cells to NeuN had decreased on day 30 (79.3%±2.8% vs 69.0%±3.4%, t =5.871, P < 0.01 )and day 45 (87.7% ±4.6% vs 78.3%±2.4%, t =4.403, P < 0.01) in PSD animals. There was a statistically significant increased proportion of BrdU-positive cells co-stained with GFAP in PSD animals compared with the ischemia ones on day 30 and45 (t =4.226, 8.945, both P < 0.01). Conclusion CMS following ischemia exerts an inhibitory effect on hippocampal survival of new born cells as well as their differentiation into neurons, while promotes new born cells differentiating into astrocytes.