Effects of the tricyclic antidepressant clomipramine on plasma glucose levels in mice were studied. Clomipramine at doses ranging 5 – 20 mg/kg elicited significant hyperglycemia in mice. Hyperglycemia elicited by clomipramine was not reduced by pretreatment with the 5-hydroxytryptamine (5-HT) depleter p-chlorophenylalanine. The 5-HT_1/2/5/7-receptor antagonist methysergide and the 5-HT_2A/2B/2C-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT_1A/1B-receptor antagonist (−)-propranolol and the 5-HT_3/4-receptor antagonist tropisetron did not affect it. The 5-HT_2B/2C-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the 5-HT_2A-receptor antagonist ketanserin was without effect. Clomipramine-induced hyperglycemia was reduced by prior adrenalectomy. These results suggest that clomipramine induces hyperglycemia in mice by blocking the 5-HT_2B and/or 5-HT_2C receptors, which results in facilitation of adrenaline release.