The aim of this study was to compare the effect of Salix aegyptiaca extract and Fluoxetine in reducing depression. In this experimental study used 60 laboratory mice weighting approximately 25 to 30 grams. Mice were divided in to the six groups: control, depression, Fluoxetine and three groups received different doses of 50, 100 and 200 mg/kg intraperitoneal injection of hydro alcoholic Salix aegyptiaca extract. After intraperitoneal injection, Forced swimming test and the tail suspension test was used to determine the level of depression. Mobility and immobility time of mice in each test indicates animal level of depression. The results were analyzed using humanities statistical software. The results showed that Salix aegyptiaca extract at a dose of 200 mg/kg was significantly effective in increasing mobility time in both tests compared with control and fluoxetine groups, indicating depression improvement. According to the results, Salix aegyptiaca hydro alcoholic extract with a dose of 200 mg/kg can be a good alternative to fluoxetine and can be utilized in reducing depression symptoms.