OBJECTIVE： To observe therapeutic efficacy and safety of escitalopram and fluoxetine in the treatment of depression. METHODS： 106 patients with depression were randomly divided into observation group and control group with 53 cases in each group. Observation group was given escitalopram 10-20 mg， qd， and control group was given 20-40 mg， qd. Both groups were treated with 6 weeks. The levels of IL-2， IL-6， TNF-α and Hcy were observed in 2 groups， and HAMD and TESS were recorded in 2 groups. RESULTS： Total effective rate of observation group （86.79％） was higher than that of control group （77.36％）， with statistical significance （P＞0.05）； after treatment， the levels of IL-2， IL-6， TNF-α and Hcy decreased significantly in 2 groups， the observation group was lower than the control group， with statistical significance （P＜0.05）. After treatment， emotion， mental anxiety， sleep disorder， cognitive disorder， somatic anxiety score and HAMD total score all decreased significantly in 2 groups， the observation group was significantly lower than the control group， with statistical significance （P＜0.05）. TESS score of observation group was significantly lower than that of control group 3 weeks and 6 weeks after treatment， with statistical significance （P＜0.05）.  CONCLUSIONS： Escitalopram is similar to fluoxetine in the treatment of depression， but escitalopram can improve inflammatory response significantly and decrease the level of Hcy with mild ADR.