The mGlu5 receptor antagonist 2-methyl-6-(phenylethylnyl)-pyridine (MPEP) is highly anxiolytic in rodent models of anxiety. Recent studies showed that MPEP remains effective in some models of anxiety after repeated treatment, but tolerance may develop in other models. To further evaluate anxiolytic properties of repeated MPEP, a single administration of 3, 10, or 30 mg/kg p.o. and repeated administration of 30 mg/kg p.o. was tested in the stress-induced hyperthermia model in mice. MPEP dose-dependently inhibited stress-induced hyperthermia when given acutely. MPEP remained equally active in reducing stress-induced hyperthermia after five daily treatments with 30 mg/kg, further validating MPEP as a potential anxiolytic for chronic use.