Atherosclerosis being considered as an inflammatory disorder, the present study was undertaken to investigate the effectiveness of anti-inflammatory drugs (ibuprofen, aspirin, and celecoxib) in hypercholesterolemia. Ibuprofen is a cyclooxygenase (COX-1 and COX-2) inhibitor known to reduce the production of prostaglandins that play prominent role in inflammation. Beside the anti-inflammatory effects that make ibuprofen interesting for the treatment of condition associated with hypercholesterolemic atherosclerosis. Various other properties of ibuprofen were investigated, ibuprofen showed better reduction in total cholesterol, triglycerides, very low density lipo-protein, low density lipo-protein and atherogenic index than aspirin and celecoxib in hypercholesterolemic animals. These properties of ibuprofen may be due to inhibition of acetyl-CoA carboxylase initiating the synthesis of fatty acids. Ibuprofen significantly elevated antioxidant (super oxide dismutase; catalase) levels and reduced lipid peroxidation. Ibuprofen inhibits COX enzymes and thereby inhibits generation of free radicals during prostaglandins synthesis, which may be responsible for reduction in lipid peroxidation, super oxide dismutase levels and for high catalase levels. Interestingly, ibuprofen decreased total leukocyte count, monocyte count, erythrocyte sedimentation rate and C-reactive protein levels. From the results of present study, it can be concluded that ibuprofen (non-selective COX inhibitor) showed promising antihyperlipidemic, antiatherosclerotic, antioxidant, antiinflammatory and non-ulcerogenic activity in atherosclerotic animals as compared to aspirin (preferential COX-1 inhibitor) and celecoxib (selective COX-2 inhibitors, suggesting the inducible role of COX in atherosclerosis.