Cholesterol efflux from lipid-loaded cells is a key event associating with stability and subsidence of plaque. There are many proteins and factors participating in regulation of cholesterol efflux of lipid-loaded cells, which is very complex. We propose,by summarizing the recent research,a novel mode of “four systems and one center with coupling transportation and networking regulation". The novel mode consists of 1) intracellular trafficking system of caveolin-1 complex,2) transmembrane transporting system of ATP binding cassette transporter(ABC)-A1 complex,3) transmembrane transporting system of scavenger receptor (SR-) B1 complex,4) extracelluar trafficking system of high density lipoprotein/apolipoprotein (HDL/Apo)-A1 and 5) caveolae transporting center. In brief,caveolin-1 complex system transports cholesterol from intracellular compartments to caveolae; both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to HDL/Apo-A1. There are networking regulation among four systems. This mode provides a simple and concise way to understand the dynamic process of atherosclerosis.