In this study, we investigated whether glucagon-like peptide-2 (GLP-2) had antidepressant-like effects in mice, and whether these activities were associated with monoamine systems in mice. Antidepressant-like effects were evaluated based on the immobility time in the forced-swim test. GLP-2 (1.5–6μg/mouse, i.c.v.) significantly reduced the immobility time in a dose-dependent manner without affecting locomotor activity in the wheel running test and memory function in the step-down passive avoidance test. These effects were inhibited by pretreatment with metergoline (an antagonist of non-specific 5-HT receptors), parachlorophenylalanine (an inhibitor of 5-HT synthase), NAN-190 (an antagonist of 5-HT 1A receptors), yohimbine hydrochloride (an antagonist of α 2 adrenoceptors), atenolol (an antagonist of β 1 receptors), and raclopride (an antagonist of D 2 receptors), but not prazosin (an antagonist of α 1 adrenoceptors), ICI118551 (an antagonist of β 2 adrenoceptors), and SCH23394 (an antagonist of D 1 receptors). These results suggest that GLP-2 exerts antidepressant-like effects in the forced-swim test in mice, which are associated with 5-HT 1A , α 2 , β 1 and D 2 receptors.