Objective To study the influence of red blood cell (RBC) deformability on blood flow, so as to make the blood flow simulation more accurately. Methods Based on analysis of rheological properties of blood and mechanical properties of RBCs, the existing two-phase flow model of blood was improved, and the effect of non-inertial lift force generated by the interaction between soft RBCs and shear flow or the vessel wall was considered in the improved model. The blood flow in vessels with different diameters was simulated by using this improved model. Results The radial motion of RBCs generated by non-inertial lift force had an obvious influence on the distribution of RBC volume fractions and blood velocity. When the vessel diameter was between 0.1-3.0 mm, the simulated relative viscosity of blood by the improved model was very close to the measured viscosity. Conclusions The non-inertial lift force is one of the main reasons leading to Fahraeus-Lindqvist effect of blood, and the improved model considering the non-inertial lift force can simulate the blood flow more accurately, which provides a more accurate method for the simulation of vascular system treatment and cell sorting.