Inflammation causes debilitating mandatory to the human physic, also the marketed allopathic drugs exhibits a side effects. Main background to minimize the side effects by treating ayurvedic drugs which are available in the naturals. The study was intended to evaluate the antiinflammatory activity of ethanolic extract of leaves of Pupalia lappaceae Juss. (Amaranthaceae) (EEPL) in Wistar strain rats and the toxicity studies was intended in Swiss Albino mice. Phytochemical analysis was carried out by using standard methodology to analyze the major phytoconstituents. The anti-inflammatory activity was carried out in different methods such as carrageenan, cotton pellet, croton oil, histamine and serotonin induced oedema. Different doses (100 and 300 mg/kg/i.p.) of EEPL was injected to rats and the results compared with standard drug indomethacin (10 mg/kg). Paw volume was measured using digital plethysmometer. The plant has alkaloids, amino acids, glycosides, flavonoids, saponins, starch, steroids, tannins and terpenoids. The EEPL showed the maximum inhibitory activity at 300 mg/kg/i.p. in a dose dependent manner. These inhibitions were statistically significant (p<0.01-0.001). The significant values are intended to investigate the chemicals present in the extract of EEPL. EEPL was analyzed its chemical compounds by GC-MS (Gas Chormatography and Mass Spectrum). The major chemical compounds were eluted as phytol, mesitylene and etc. These results indicated that EEPL is a bioactive agent and having significant results in anti-inflammatory action by inhibition of the exudation, and leukocytes recruitment into the inflamed tissues.