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Atherosclerosis is a chronic progressive disease leading to cardiovascular disease. Leukotrienes are potent mediators of inflammation derived from Arachidonic Acid. AA may be released from phospholipid in the cell membrane of intact cells following stimulation, infection or injury by the action of cytosolic phospholipase A2.This enzyme increased the risk of CHD, stroke and vascular death.A total of 300 natural compounds were found from different sources of plants.Each of these compounds were screened by Lipinski's Rule of 5, among these 200 of them were selected, the molecules are subjected to docking analysis with the target phospholipase A2.The compound having the least docking score was selected. The top 20 least score was screened for toxicity analysis.Then,the compound & the target was analyzed for binding site.From the active site analysis it was known that amino acids like His, Leu, Asp, Pro, Asn, Gln,Glu was present in Site 6 which shows most prominent sites. Later the pathway analysis was done using Cell Designer.The insilico docking results that 13 natural compounds was found to be the best lead compounds for the disease.