Objective To evaluate the effect of ethyl acetate extract of Adenema hyssopifolium (AHEAE) on normal body temperature and brewer's yeast-induced pyrexia rats. Methods Preliminary phytochemical tests, acute toxicity tests and antipyretic evaluation were carried out in ethyl acetate extract of Adenema hyssopifolium. Two doses of the extract (300 or 600 mg/kg orally) and standard antipyretic agent, paracetamol at a dose of 150 mg/kg were administered to various group of the rats. Mean rectal temperature before and after treatment was noted. Results The phytochemical analysis of AHEAE revealed the presence of flavonoid and iridoid glycosides as major phytoconstituents. The administration of AHEAE at a dose of 300 or 600 mg/kg produced significant reduction (P<0.001 and P<0.01) of the body temperature in normal and pyrexia rats on a dose dependent manner. The antipyretic influence of AHEAE was comparable to that of standard antipyretic agent, paracetamol (150 mg/kg), and onset of action and reduction in pyrexia towards normal body temperature was delayed when compared to paracetamol treatment. At dose of 600 mg/kg, AHEAE reduced pyrexia to normal body temperature at 4 h after its administration compared to reduction of pyrexia to normal body temperature at 2 h by standard drug. The reduction of fever was consistent in paracetamol group from 2 to 4 h after its administration to normal body temperature compared to AHEAE treatments. Conclusions Our present results corroborate with the traditional notion of Adenema hyssopifolium G. DON that is being used as an effective cure of fever and add authenticity to claim of indigenous healers that the taxon is a potential antipyretic agent.