To optimized the establishment of a model of depression in vitro，and to explore the protective effects of Crocus sativus L on PC12 cell injury induced by CORT and its related mechanisms.Methods:PC 12 cells were treated with CORT in different concentrations (0，125，250，500，750 and 1 000 μmol/mL) for 24，36 and 48 h to establish a depression model in vitro.PC12 cells were pretreated with Crocus sativus L at different concentrations (2.5，5 and 10 ug/mL) for 24 hours.Cell viability was measured by CCK-8，and the protective effects of Crocus sativus L on PC12 cell injury induced by CORT were determined.The levels of LDH activity in supernatant were detected to judge the protection effect of the drugs on PC12 cells.The protective effect on PC12 apoptosis was analyzed by Annexin V-FITC/PI staining.Caspase-3 activity was detected in cell lysates and correlation between drug action and Caspase protein pathway was judged.Results:After CORT (0-1 000 μmol/L) treatment of PC12 cells for 24 h，the cell survival rates of each concentration were decreased with dose increasing in a dose-dependent manner.When the concentration of Crocus sativus Lextract was greater than 100 μg/mL，the effect on PC12 cells was statistically significant.After drug pretreatment，the PC12 cells survival rate was increased from model group (53.31±4.18)% to (57.46±2.76)%，(60.48±2.73)%，(61.99±3.05)%，(61.38±2.26)%，(59.46±2.41)% and (58.64±3.74)%，respectively.The release of LDH from Crocus sativus L pretreated group was significantly lower than that of model group (P<0.05).Crocus sativus L can significantly inhibit CORT-induced apoptosis of PC12 cells.Crocus sativus Lcan inhibit the expression of Caspase-3.Conclusion:Crocus sativus L has the protective effects on PC12 cell injury induced by CORT.