Traditional herbal healers "Hakims" use various plants of the Cholistan desert, Pakistan for treating a number of infectious and non-infectious diseases. However, there has never been a scientific validation of these plant-based therapeutics. We compared the antipyretic effect of Echinops echinatus, Alhagi maurorum, Fagonia cretica, Cymbopogon jwarancusa and Panicum turgidum in animal model. These plants were used to reduce E.coli lysate induced pyrexia in rabbits. There were five groups of rabbits having five rabbits in each group. Among these five groups, three received various doses of experimental treatment, paracetamol was given to fourth group known as positive control. The fifth group of animals served as negative control and received no treatment. Ethanol extracts of Fagonia cretica (500 mg/kg), Panicum turgidum (500 mg/kg and 750 mg/kg), Alhagi maurorum (500 and 750 mg/kg), Cymbopogon jwarancusa (250 mg/kg) and Echinops echinatus (750 mg/kg) showed significant antipyretic effects when compared with controls and experimental counterparts. These results revealed that ethanol extracts of the plants evaluated in this study have dose dependent antipyretic activity. Further detailed screening of these plant species is recommended.