Cholesteryl　ester　transfer　protein　(CETP)　mediates　cholesteryl　ester　(CE)　transfer　from　the　atheroprotective　high　density　lipoprotein　(HDL)　cholesterol　to　the　atherogenic　low　density　lipoprotein　cholesterol.　In　the　past　decade,　this　property　has　driven　the　development　of　CETP　inhibitors,　which　have　been　evaluated　in　large　scale　clinical　trials　for　treating　cardiovascular　diseases.　Despite　the　pharmacological　interest,　little　is　known　about　the　fundamental　mechanism　of　CETP　in　CE　transfer.　Recent　electron　microscopy　(EM)　experiments　have　suggested　a　tunnel　mechanism,　and　molecular　dynamics　simulations　have　shown　that　the　flexible　N-terminal　distal　end　of　CETP　penetrates　into　the　HDL　surface　and　takes　up　a　CE　molecule　through　an　open　pore.　However,　it　is　not　known　whether　a　CE　molecule　can　completely　transfer　through　an　entire　CETP　molecule.　Here,　we　used　all-atom　molecular　dynamics　simulations　to　evaluate　this　possibility.　The　results　showed　that　a　hydrophobic　tunnel　inside　CETP　is　sufficient　to　allow　a　CE　molecule　to　completely　transfer　through　the　entire　CETP　within　a　predicted　transfer　time　and　at　a　rate　comparable　with　those　obtained　through　physiological　measurements.　Analyses　of　the　detailed　interactions　revealed　several　residues　that　might　be　critical　for　CETP　function,　which　may　provide　important　clues　for　the　effective　development　of　CETP　inhibitors　and　treatment　of　cardiovascular　diseases.