Objectives To analyze the clinical efficacy of escitalopram and fluoxetine in the treatment of depression and the influence on serum brain-derived neurotrophic factor（ BDNF） and inflammatory response factor. Methods A total of 118 patients with depression admitted to the psychiatric department of our hospital from January 2017 to November 2018 were recruited as the research subjects. All the subjects were assigned to observation group（ n=59） and control group（ n=59） by random number table method. The control group was treated with fluoxetine， while the observation group was treated with escitalopram. The treatment lasted for 6 weeks. The clinical effects of the two groups were observed after treatment， and the two groups were compared before and after on serum levels of BDNF， neurological function-related factor（ S100B） and inflammatory reaction factors， including interleukin-2， 6（ IL-2， IL-6） and tumor necrosis factor-alpha（ TNF-α）. The changes of Hamilton Depression Scale（ HAMD） score and Treatment Emergent Symptom Scale（ TESS） score were recorded before and after treatment. Results The total effective rate was 86.44% in the observation group and 76.27% in the control group. There was no statistical significance in the difference between the two groups（ P＞ 0.05）. After treatment， the level of serum BDNF increased significantly than before， while the level of S100B decreased（ P＜0.01）. The level of BDNF of the observation group is higher than that of the control group， while the level of S100B is lower after treatment（ P＜0.01）. After treatment， the levels of IL-2， IL-6 and TNF-α in the two groups were significantly lower than those before treatment. The levels of inflammatory factors in the observation group after treatment were significantly lower than those in the control group（ P＜0.01）. After 3 and 6 weeks of treatment， HAMD scores in both groups were significantly lower than those before treatment（ P＜0.01）. The HAMD score of the observation group was significantly lower than that of the control group after 3 weeks of treatment （P＜ 0.01）， however， there was no significant difference in the HAMD score between the two groups after 6 weeks of treatment（ P＞0.05）. The TESS score of the observation group was slightly lower than that of the control group during the treatment period， but there was no statistical significance（ P＞0.05）. Conclusions Escitalopram and fluoxetine are both effective and safe in the treatment of depression. Compared with fluoxetine， the level of serum BDNF in patients treated with Escitalopram is significantly higher， the level of inflammatory factors is significantly lower and the effect is faster.