Apolipoprotein E (apoE) has high affinity for the cell surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma chylomicron clearance, a transgenic mouse line which overexpresses apoE in the intestine was established. Immunohistochemistry demonstrated that considerable amounts of apoE were localized to mucosal cells of the intestine. In an oral retinyl palmitate challenge test, both the peak height and area under the curve in transgenic mice were less than 25% of those in controls. We speculate that the apoE molecules produced in the intestine of transgenic mice were incorporated onto newly synthesized chylomicron particles before their secretion into the plasma and thereby contributed to rapid plasma clearance of chylomicron remnants. Gene expression of apoE in the intestine would be a promising way to control postprandial hyperlipemia.