The purpose of this study was to investigate the effects of Rhodiola rosea extract and depression on the serotonin (5-HT) level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats induced by Chronic Mild Stress (CMS). Seventy male Sprague-Dawley rats were divided into seven groups (10 per group): normal control group, untreated depressive rat model group, negative control group, positive control group, low dosage Rhodiola rosea extract (1.5g/kg) group, medium dosage Rhodiola rosea extract (3g/kg) group and high dosage Rhodiola rosea extract (6g/kg) group. After the depressive rats induced by CMS had received Rhodiola rosea extract for 3 weeks, the 5-HT levels at cerebral hippocampus were detected by high performance liquid chromatography. Bromodeoxyuridine (BrdU) was injected in vivo to label the proliferating cells at hippocampus, and morphometry was used to count the hippocampal neurons. The results showed that the 5-HT level of the three experimental groups had recovered to normal status. The immunohistochemistry of hippocampus BrdU positive cells had returned to the normal level in the group of depressive rats with low dosage Rhodiola rosea extract. In conclusion the results demonstrated that Rhodiola rosea extract could improve 5-HT level in hippocampus in depressive rats, and low dosage Rhodiola rosea could induce neural stem cell proliferation at hippocampus to return to normal level, repairing the injured neurons at hippocampus.