Abstract: With the continuous exploration of blood microfluidic processes, the microscopic characteristics of red blood cells (RBCs) in microchannels have attracted attention. Using low-damage methods based on fluid mechanics to regulate cell volume and complete transmembrane drug transfer has gradually become a research hotspot. To further explore the mass transfer and mechanical properties and their influencing factors for RBCs in microchannels, this paper adopts the immersion boundary method to study the entire movement process of cells crossing narrow channels. By supplementing the osmotic slip velocity term on the surface of the cell membrane, the mass transfer process is coupled with cell movement, achieving numerical analysis of the microscopic mass transfer characteristics of red blood cells in narrow channels. The result shows that during the process of cells into and out of the slit, the volume undergoes a process of first loss and then recovery. In this process, the head and tail of the cell mainly penetrate outward, while the middle part mainly infiltrates inward. Furtherly, research suggests that the change in cell volume caused by the difference between inward and outward permeation rate dominantly, not the difference between the membrane area of inward and outward permeation. After exploring the influencing factors of volume changes, we found that narrow channels and larger inlet and outlet angles can cause more volume loss and recovery of cells. When other factors remain unchanged, the larger the outlet angle, the smaller the stable volume of cells after leaving the slit. Additionally, the more the hardness of the cell and the greater the permeability (permeability coefficient) of the cell membrane, the higher the volume loss and recovery degree of the cell during movement in the slit.