Abstract: Objective：To explore the changes of erythrocyte deformability and possible mechanisms of rats suffering from hyperlipidemia induced by high-fat diet. Methods ：Sixteen rats were randomly divided into two groups: the control group and the hyperlipidemia group. The control group animals were fed with standard laboratory chow; the hyperlipidemia ones were fed with high-fat diet. Sixteen weeks later, blood was draw by abdominal aortic puncture, anti-coagulated with heparin. Then the plasma TG and Ch, erythrocyte deformation index, orientation index, and membrane fluidity were measured; and erythrocyte skeleton was observed with a laser confocal microscopy. Results：Compared with the control group, deformation index, orientation index, and membrane fluidity decreased significantly in rats with hyperlipidemia（P<0.05）; moreover, the integrity of cytoskeleton was destroyed and the contents of F-actin reduced significantly（P<0.05） as well. Conclusion：