Objective To investigate the anti-depressant effects of psoralen and its mechanisms. Methods The anti-depressant effects of psoralen were evaluated by the forced swimming tests in rats and mice and the tail suspension test in mice. The animals were randomly divided into four groups： control group， low dose psoralen group， high dose psoralen group and amitriptyline group. The effects of psoralen on immobility time were measured in the forced swimming test and tail suspension test in rats and mice. Likewise， PC12 cells injury was induced by corticosterone and the effects of psoralen on the cell viability were measured by MTT assay. Results Psoralen significantly decreased the immobility time in the forced swimming tests and tail suspension test in rats and mice， which were significantly different compared with the control group（ P＜0.05）. In addition， psoralen could improve the survival rate of PC12 cells injuried by corticosterone. Conclusions Psoralen has anti-depressant effects and its mechanisms may be involved in the protective effects of neural cells.