Sepsis, a common cause of morbidity and mortality in critically ill patients, is associated with systemic inflammatory response syndrome due to upregulation of cyclooxygenase-2 and increase in the levels of PGE2. It is also associated with increase in the levels of proinflammatory cytokines like TNFα and IL-1β. Calotropis procera is a plant that grows in the wild producing latex. The aqueous and methanolic extracts of dried latex of this plant (AqDL and MeDL) and proteins isolated from the fresh latex (LP) have shown anti-inflammatory and anti-arthritic properties. AqDL and MeDL are orally effective, LP is effective parenterally. The current study was designed to evaluate the efficacy of these extracts against yeast-induced pyrexia and the levels of TNFα and PGE2 in the hypothalamus of rats.