It has been demonstrated that the aqueous extract of Tagetes lucida Cav. shows an antidepressant-like effect on the forced swimming test (FST) in rats. The aim of this study was to analyze the participation of the serotoninergic system in the antidepressant-like effect of the aqueous extract of T. lucida. Different doses of the extract of T. lucida were administered at 72, 48, 24, 18 and 1h before FST. The animals were pretreated with a 5-HT1A receptor antagonist (WAY-100635, 0.5mg/kg), a 5-HT2A receptor antagonist (ketanserin, 5mg/kg), a β-noradrenergic receptor antagonist (propranolol, 200mg/kg), and with a α2-noradrenergic receptor antagonist (yohimbine, 1mg/kg) alone or combined with the extract and pretreated with a serotonin synthesis inhibitor (PCPA) before treatment with 8-OH-DPAT + the extract of T. lucida. In addition, suboptimal doses of the 5-HT1A agonist (8-OH-DPAT) + non-effective dose of extract was analyzed in the FST. To determine the presence of flavonoids, the aqueous extract of T. lucida (20µl, 4mg/ml) was injected in HPLC; however, a quercetin concentration of 7.72mg/g of extract weight was detected. A suboptimal dose of 8-OH-DPAT+extract of T. lucida decreased immobility and increased swimming and climbing. An antidepressant-like effect with the aqueous extract of T. lucida at doses of 100 and 200mg/kg was observed on the FST with decreased immobility behavior and increased swimming; however, this effect was blocked by WAY-100635, ketanserin and PCPA but not by yohimbine and propranolol, suggesting that the extract of T. lucida could be modulating the release/reuptake of serotonin.