Pyrexia or fever is caused as a secondary impact of infection, malignancy or other diseased states. It is the body's natural defense to create an environment where infectious agent or damaged tissue cannot survive. In present study, the antipyretic activity of ethanol extracts from Agave sisalana was evaluated using Brewer's yeast induced pyrexia in rats. The results showed that the ethanolic extract of Agave sisalana possesses a significant antipyretic effect in maintaining normal body temperature and reducing yeast-induced elevated body temperature in rats in a dose dependent manner and its effect is comparable to that of the standard antipyretic drug paracetamol. It was therefore concluded that the extracts of Agave sisalana demonstrated antipyretic activity, the ethanol extract was found to be potent than the aqueous extract. Key words: Agave sisalana, Ethanolic extract, Antipyretic activity.