In this study, we investigated the possible antidepressant-like effect ofI. paraguariensisin rats. Rats were treated for four weeks with an aqueous extract ofI. paraguariensisin drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours ofI. paraguariensisintake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile ofI. paraguariensisextract.I. paraguariensisreduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect ofI. paraguariensiswas observed in rats through the elevated plus-maze test. The antidepressant-like effect ofI. paraguariensiswas not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract ofI. paraguariensisdecreases the time of immobility in rats suggesting an antidepressant-like effect.