Objective_Some clinical studies have found alterations in the levels of serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) after applying antidepressant treatment in patients with major depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and after 12 weeks of antidepressant treatment in MDD outpatients. Methods_Serum BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and after 12 weeks of treatment. The severity of depression was measured with the Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment was defined as a posttreatment HAMD-17 score of <7. Results_Among MDD patients, 19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients had significantly higher serum BDNF and GDNF levels at baseline than those after 12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did not significantly between the remission and nonremission groups. The significant alteration in both BDNF and GDNF levels after antidepressant treatment were observed in patients with remission. Conclusion_The present study suggests that the baseline serum BDNF and GDNF levels are higher than the posttreatment levels in some mild-to-moderate MDD outpatients and the significant alteration in BDNF and GDNF level after treatment were observed in patients with remission.