Anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in several studies. Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class that is not related to benzodiazepines, unlike most drugs predominately used. The purpose of the present study was to examine interaction between magnesium (Mg) and buspirone as a partial agonist of 5-HT_1A receptors in producing anxiolytic-like activity in the elevated plus maze. The anxiolytic-like effect of Mg (50, 100 and 200 mg/kg, orally), buspirone (5 mg/kg, i.p) and its interaction with Mg (50 mg/kg) was evaluated after ten days treatment. Mg given at all doses (50, 100 and 200 mg/kg) and buspirone (5 mg/kg) induced an anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms (%OAT), the percentage of the open arm entries (%OAE) and number of total entries. Percent time spend in open arms was reduced when buspirone coadministered with Mg (50 mg/kg) compared to Mg alone. However, the number of entries did not change significantly. No synergistic interaction (increased time in open arms and number of open arm entries) between Mg and buspirone was observed, in this test, on the contrary, %OAT preserved about buspirone effects and %OAE remained around Mg effect. The obtained data indicate that Mg may act partly via serotonergic receptors due to buspirone’s inhibitory action as a partial agonist of serotonin receptor.