Whether benzodiazepines (BZD) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncer tain.The present study designed four preclinical experiments to determine the effects of BZD using chronic unpredictable stress model.In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers.Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3week.In Experiment 2, mice received p.o.administration of three diazepam dosages prior to each variate stress session for 4week.This treatment significantly antagonized the elevation of stress-induced corticosterone levels.Diazepam 0.5 and 1 mg·kg-1 blocked the detrimental effects of chronic stress.In Experi ment 3, after 7 week of stress sessions, daily po diazepam ad ministration during 1 week recovery phase dose-dependently ac celerated the recovery of stressed mice.In Experiment 4, 1 week diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant like behavioral effect, whereas 4 week diazepam administration produced opposite effects.Hence, diazepam can slow the pro gress of chronic stress-induced detrinental consequences by nor rmalizing glucocorticoid hormones.Considering the adverse effect of long-term diazepam administration on hippocampal plasticity,the preventive effects of diazepam may depend on the proper dose.Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress.