Objective To explore the effects and mechanisms of escitalopram on the expression of glial cell line-derived neurotrophic factor(GDNF) in hippocampus of depression model rats.Methods 40 male SD rats were randomly divided into four groups:control group(group A),control + escitalopram group (group B),depressive group (group C),and depressive + escitalopram group (group D).Chronic mild unpredicted stress (CUMS)with solitary condition was taken to establish rat depression model.And the group B and D were treated with intragastric admistration of escitalopram(10 mg · kg-1 · d-1),the group A and C with sodium chloride.The open-field test and sucrose consumption were used to evaluate the depression behaviors of rats.The apoptotic hippocampal cells were detected by TUNEL.And the expression of GDNF,Bax,Bcl-2 and Caspase3 mRNA were detected by real-time RT-PCR.Results ① Compared with group A(12.0 ± 1.83),the number of apoptotic cells in hippocampus was significantly increased in group C (19.3 ± 1.77) (P ＜ 0.01),while group B (11.9 ± 1.91) was no significant difference (P＞ 0.05).Compared with group C,the group D(12.7 ± 1.77) had a significant reduction in the number of apoptotic cells (P ＜ 0.01).②Compared with group A,GDNF and Bcl-2 mRNA expression was decreased (P ＜ 0.01),but Bax and Caspase3 mRNA expression was both increased significantly in group C(P＜0.01) ;while in group D,GDNF and Bcl-2 mRNA expression was higher (P ＜0.01),but Bax and Caspase3 mRNA expression was lower than that in group C (P ＜0.01).Conclusion Escitalopram can improve depressive behaviors and reduce hippocampal apoptosis,which maybe associate with increasing GDNF protein and mRNA expression,and promoting the regeneration of neurons,up-regulating of mRNA Bcl-2 expression,and down-regulating of mRNA Bax and Caspase3 expression.Finally it may prevent the neuronal apoptosis in hippocampal and play the role of cerebral protection.