Areca catechu L. extracts I and II, prepared using two different solvent systems, exhibited strong inhibitory activities against pancreatic cholesterol esterase (pCEase) in vitro. To determine their cholesterol-lowering effects, these two extracts were investigated by analyzing plasma lipid levels, intestinal enzyme activities, and the absorption of cholesteryl oleate. For 6 days, male rats were fed a diet containing cholesteryl oleate (0.5 g/100 g of body weight) either with or without the Areca nut extract supplements. The supplementation of the two Areca nut extracts significantly lowered the concentrations of plasma cholesterol by 13. 4 and 11.7% and plasma triglycerides by 35.0 and 36.9%, respectively, compared with the pre-experimental values. However, when the cholesteryl oleate diet was fed without any Areca nut extract in high-cholesterol control, the plasma cholesterol and triglyceride concentrations significantly increased by 13.6 and 15.9%, respectively, compared with the pre-experimental values. After 6 days of treatment, the intestinal pCEase activities were significantly lower in the groups supplemented with the Areca nut extracts (37.8 and 26.5%) than in the group with no extract supplement (83.2%). The supplements also significantly elevated the excretion of [1,2(n)-(3)H]cholesteryl oleate administered orally, when determined by the large intestinal contents, 930.5 Bq/day (Areca I) and 1,766.3 Bq/day (Areca II) vs. 98.1 Bq/day (high-cholesteryl oleate (CO) control). The inhibition of pCEase activity with the supplementation of the Areca nut extracts could account for the decrease in [1,2(n)-(3)H]cholesteryl oleate absorption that resulted in decreased radioactivity in blood.