The effects of hematocrit (Hct) on blood flow in microcirculation were investigated by computer simulation using a particle method. Deformable red blood cells (RBCs) and blood plasma were modeled by assembly of discrete particles. It was assumed that an RBC consisted of an elastic membrane and inner viscous fluid, and that plasma was viscous fluid. The particles for the RBC membrane were connected with their neighboring membrane particles by stretch/compression and bending springs. The motion of all the particles that was subjected to incompressible viscous flow was solved by the moving particle semi-implicit (MPS) method based on Navier-Stokes (NS) equations. The forces induced by the springs to express the elastic RBC membrane were substituted into the NS equations as the external force, which enabled coupled analysis of elastic RBC motion and plasma fluid flow. Two-dimensional simulations of blood flow between parallel plates were carried out for various Hct values. As a result, it was shown that at higher Hct, RBCs were less deformed into a parachute shape during their downstream motion, indicating that mechanical interaction between RBCs restricted the RBC deformation. Mechanical interaction between RBCs had a significant influence on RBC deformation and the velocity profile of plasma flow when the Hct value was more than 0.20∼0.30. Apparent blood flow resistance increased with Hct, corresponding to previously reported in vitro experimental results compiled to an empirical formula.