In recent years, with socioeconomic development, changes in lifestyle, diet and the aging of the population, the incidence of hyperlipidemia has been increased. Actually, it is one of the most important public health problems which threats human health worldwide and is associated with excessive medical expenses. Hyperlipidemia is an asymptomatic chronic condition commonly characterized by an excess of lipid profiles in the bloodstream, it can silently hurt the blood vessels, heart, brain, and kidneys. Thus, these patients have a significant and recognized risk factor for progression of atherosclerosis, cardiovascular and cerebrovascular diseases. Cholesterol is a fatty substance which is circulate in the blood and has an essential role in the body as protection for the vascular walls, linings of body organs, digestive function and a component in forming cell membranes and some hormones. But, it can also be a problem, if too much used through the diet and not metabolized or used. High level of cholesterol has been shown to destroy vascular function and structure and leading to accumulation of fatty plaques on vessel walls, narrowing veins and arteries and decreased blood flow to the heart muscle, brain, and other organs or leading to embolism. In addition, high cholesterol cause to oxidative change, which has an augmentative role in the formation of atheroma plaques in vessels wall. Generally, hyperlipidemia diagnosed by confirmed in individuals with blood cholesterol levels of >200 mg/dl or blood triglyceride levels of >180 mg/dl. Controlling hyperlipidemia also have a vital role in the prevention of hypertension, myocardial infarction, risk of stroke, coronary deaths, and overall mortality. Although, a healthy lifestyle, weight loss, and decreased dietary cholesterol have been shown to lower the risk of developing hyperlipidemia. If these interventions are not efficient, drug therapy will be necessary in decreasing hyperlipidemia. Many anticholinergic adverse effects such as weight gain or weight loss, nausea, constipation, sedation, cardiac toxicity, orthostatic hypotension, arrhythmias, sexual dysfunction and many drug interactions may occur with antihyperlipidemic medicines. At the present years, the interest for herbal remedies as an important factor for treatment and maintenance of health is increasingly emphasized. The use of herbal remedies becomes wide spread in the world due to their low expense, availability, less side effects and drug interactions compared to the chemical drugs. Lactuca sativa commonly known as lettuce, is a plant species belonging to the family Asteraceae. It is most often grown as a leaf vegetable and sometimes for its stem and seeds. It is a very popular herb for salad and food. In recent pharmacological studies, lettuce has demonstrated antidiabetic, narcotic, antioxidant and anti-inflammatory activities. Phenolic acids, flavonoids, anthocyanins, and vitamins A and C are the major active compounds in lettuce. Some well-designed clinical trials have indicated the efficacy of lettuce in sleep disorder, anxiety and diabet. In this study, we investigated the hypolipidemic effect of chronic administration of aqueous ethanol extract of lettuce seed in a 12-week double-blind, placebo-controlled and randomized clinical trial. The data suggested that lettuce extract has hypolipidemic properties and should be further investigated as a potential intervention for hyperlipidemic treatment in patients.