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This study was designed to investigate whether or not onion peel extract can lower blood lipid levels in rats exposed to cigarette smoke (CS) extract with a high-fat diet. Initially, male Sprague-Dawley rats were housed individually in a stainless steel, wire-bottomed cage with free access to AIN-93G diet. Rats were weight-matched and assigned to the following five groups: 1) control rats (CT) fed standard AIN-93G diet alone, 2) control rats exposed to CS extract (CT+CS), 3) high-fat group (HF) fed standard AIN-93 diet supplemented with 3% lard and 0.2% cholesterol, 4) high-fat group exposed to CS extract (HF+CS) fed standard AIN-93 diet supplemented with 3% lard and 0.2% cholesterol plus CS extract, and 5) high-fat plus onion peel (OP) extract group exposed to CS extract (HF+CS+OP) fed standard AIN-93 diet supplemented with 3% lard, 0.2% cholesterol, and onion peel extract (20 mg/17 g diet) plus CS extract. Using this feeding protocol, all animals completely consumed their respective diets throughout the 6 week duration. Blood was collected via the orbital sinus at weeks 0, 3, and 6, following overnight food deprivation. OP extract feeding resulted in significant reductions in blood triglyceride, total cholesterol, and non-HDL-cholesterol. Further, serum activities of aspartate transaminase and alanine transaminase were significantly reduced by OP extract at 6 weeks. These results provide clear evidence that onion peel extract has a profound inhibitory effect on blood lipids in rats exposed to CS extract. These findings suggest that OP extract can be used as an effective means in alleviating the serum lipid concentration after CS exposure.