Ethnopharmacological relevance: The leaves and stems of Lippia multiflora Moldenke (Verbenaceae) are used in traditional medicine to treat depression, anxiety and epilepsy. Aim of the study: The present study investigated the anxiolytic-like effects of Lippia multiflora aqueous extracts in experimental models of anxiety. Materials and methods: Elevated plus maze and open field tests were used to evaluate anxiety and exploratory behaviour. The possible mechanism of action of Lippia multiflora were investigated after pretreatment of animal with agonist and antagonist of serotonin receptors, such as: mCPP, a partial agonist at the 5-HT2C receptors; Way-100635, a selective 5-HT1A receptors antagonist; and DOI, the 5-HT2A/2C receptors agonist. The levels of monoamine neurotransmitters were evaluated in the brain. Results: In the elevated plus maze, Lippia multiflora increased the number of entries into and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. These effects were blocked with the agonist and antagonist of serotonin receptors. In the open field, Lippia multiflora increased crossing and reduced rearing and defecation. The endogenous levels of noradrenaline, dopamine and serotonin in the brain homogenates remain comparable to that distilled water-treated animals. Conclusion: It could be concluded that Lippia multiflora aqueous extracts, used in traditional medicine in Cameroon for the treatment of depression, anxiety and epilepsy seemed to possess anxiolytic properties in mice. These effects might be mediated by serotonin receptors, but not by modulation of the levels of monoamine neurotransmitters when the extract is administered once after one hour.