Objective To investigate gender differences of plasma glial cell line-derived neurotro-phic factor (GDNF) levels in patients with major depressive disorder (MDD). Methods MDD subjects (male 20,female 36) and healthy controls (HCs) (male 35,female 45) were divided into four groups by gender. Plasma levels of GDNF were measured and compared in different gender groups. The clinical symp-tom severity of MDD patients was evaluated by 17-item Hamilton Depression Scale (HAMD-17) and Hamil-ton Anxiety Scale (HAMA-17). Results (1)The plasma GDNF level in male patients with major depres-sive disorder (( 1. 55 ± 0. 43 ) pg/ml ) was significantly lower than that in healthy controls (( 1. 86 ± 0. 50)pg/ml,F=4. 64,P=0. 036). There was no significant difference in GDNF level between female de-pression patients((1.62±0.46)pg/ml)) and female healthy control((1. 64±0. 48)pg/ml,F=0. 18,P=0. 672). In HCs,the GDNF level of male was significantly higher than that of female((1. 86±0. 50)pg/ml, (1. 64±0. 48)pg/ml,F=2. 04,P=0. 045). There was no significant difference in GDNF level between male and female patients(P>0. 05). (2) GDNF level in male patients with major depressive disorder was nega-tively correlated with HAMA score(r=-0. 388,P=0. 034). Conclusion The expression of GDNF is affect-ed by sex factors,which may be related to the different pathogenesis of MDD.