Siddha system of medicine is one of the oldest medical systems of India existed separately in early times. Pooram is one among the Panchasootham (five mercurial compounds) which is widely used in Siddha preparation. The main component of the Pooram is Mercury. The mercurial compound has been in use in Siddha since many centuries and it is identified and indicated for the treatment of many diseases in ancient Siddha literature. The present study was undertaken to assess the in vivo evaluation of analgesic, antipyretic and anti-inflammatory potential of Siddha formulation Natural and Synthetic Pooraparpamin rodents. The analgesic activity were evaluated through thermal (Eddy’s hot plate test) and mechanical method (Tail clip method) of pain induction in mice, whereas antipyretic activity by yeast induced pyrexia in rats. On the other hand, anti-inflammatory activity evaluated by carrageenan and cotton pellet induced inflammation in rats. Both the test drug was administered orally at the dose of 1.15 and 2.30 mg/kg, the activity was compared with a standard reference drug Indomethacin 20 mg/Kg and Paracetamol 150mg/kg. The result obtained from the study clearly demonstrates that the Siddha formulations Natural and Synthetic Pooraparpam has promising analgesic, anti-inflammatory and antipyretic activity in tested animals. Hence it was concluded that Pooraparpamis considered to be one of the safe medicine for the clinical management of fever, pain and inflammation associates medical conditions.