IntroductionAtherosclerosis, leading to myocardial infarction and stroke, is one of the most important causes of death due to cardiovascular diseases (1). The association of hypercholesterolemia with atherosclerosis is well known (2). Studies suggest that elevated lipoproteins in blood, and especially low-density lipoproteins (LDL), play an important role in the pathogenesis of atherosclerosis as indicated by their accumulation in atherosclerotic lesions (3,4). Therefore, reduction of LDL-cholesterol is an important target for the prevention and treatment of atherosclerosis.Nonsteroidal antiinflammatory drugs (NSAIDs) are used clinically as antiinflammatory, antipyretic, and antirheumatic agents (5). They exert their effect by inhibiting cyclooxygenase (COX) activity with subsequent inhibition of the formation of prostaglandins, prostacyclins, and thromboxanes (6). Several studies have shown that indomethacin or ibuprofen reduces the plasma cholesterol levels in humans or laboratory animals (7,8). Indomethacin can lower the cholesterol content of atherosclerotic blood vessels and liver in monkeys and rabbits (9), and when combined with inhibitors of angiotensin converting enzymes, indomethacin lowers blood cholesterol levels in humans (8). NSAIDs, especially flufenamic acid and indomethacin, increase LDL binding, cell association, and degradation by increasing the expression of the mRNA of the LDL receptor protein in HepG2 cells (5). Celecoxib, a selective COX-2 inhibitor, lowers plasma cholesterol during carbon tetrachlorideassociated hepatotoxicity in rats (10). Therefore, these studies suggest that COX inhibition may be useful in treating hypercholesterolemia.Reduction in the LDL levels can be achieved by the use of statins, which are the currently employed widely for the Background/aim: Hypercholesterolemia plays an important role in the development of atherosclerotic disease, which is one of the leading causes of mortality in the world. Previous studies showed that cyclooxygenase (COX) inhibitors could be used in treating hypercholesterolemia. The present study was designed to test whether COX-2 inhibition can improve lipid profiles in hypercholesterolemia.Materials and methods: Rabbits were fed a high-cholesterol diet to produce hypercholesterolemia. The role of COX-2 was evaluated using celecoxib and nimesulide. Rabbits were divided into 4 groups: the first with normal healthy rabbits, second with high-cholesterol diet and pretreatment with saline, third with high-cholesterol diet and pretreatment with celecoxib, and fourth with high-cholesterol diet and pretreatment with nimesulide. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels were measured at 2-week intervals in all the groups.Results: Results show significantly high levels of serum cholesterol, LDL, and triglyceride but low levels of HDL in hypercholesterolemic rabbits pretreated with saline. Rabbits pretreated with nimesulide and celecoxib showed improvement compared to the saline-treated gro...