In accordance with “the response to injury” theory, the entry of monocytes into the intima guided by inflammation signals, taking up cholesterol and transforming into foam cells, and egress from plaques determine the progression of atherosclerosis. Multiple cytokines and receptors have been reported to be involved in monocytes recruitment such as CCL2/CCR2, CCL5/CCR5, and CX3CL1/CX3CR1, and the egress of macrophages from the plaque like CCR7/CCL19/CCL21. Interestingly, some neural guidance molecules such as Netrin-1, and semaphorin 3E, have been demonstrated to show an inhibitory effect on monocyte migration. However, the entry and egress of monocytes from plaques is both a biochemical and biomechanical driven process. Studies elucidating the biomechanical property alteration of monocytes in the process of entry and egress from plaques will be helpful in uncovering the underlying mechanism and seeking potential therapeutic approaches for atherosclerosis recovery.