Introdution: Crocus sativus, saffron is usually used as a preservative and food ingredient. Over the past several years, therapeutic properties of saffron extract have been proven. Because of the antioxidant components of this herb, it has been candidate for some disorders as depression, considering that the effects of saffron on depression and anxiety syndromes are few, the present study aimed to investigate these aspects. Methods: In this experimental study, 36 Swiss Webster male mice with 25 to 30 g weight were randomly divided into 6 groups, negative control group, (normal saline), positive control, Fluoxetine (10mg/kg). and test groups, hydro alcoholic ethanol extract at two concentrations (50 and 100 mg/ml) alone and with fluoxetine (5mg/kg) in a mixture with [with ratio of 1: 1] (2. 5mg/kg, and 5 mg/kg of extract). All injections were done intraperitoneally as single dose a day, for 21 days, and after treatment period, swimming and tale suspension tests have been done for depression assay and Plus Maze test as model of anxiety test. Finally, one-way ANOVA was used to analyze the data using the spss 21 software. Results: The extract has shown anti-depressant effect which was in parallel with fluoxetine, almost as a dose dependent manner, but not in synergic with fluoxetine and the DATA of Plus Maze test for anxiety test, were not significant. Conclusion: According to our findings, Crocus sativus, hydroalcoholic extract has anti-depressive, but not anti-anxiety effect and has not any synergistic effect with Fluoxetine as a SSRI with anti-anxiety properties, whereby because of little adverse effects of herbal medicines, sativus crocus can be introduces as a safe cotreatment for depression disorders.