A 3D meso-scale simulation model was developed to study the failure behavior of reinforced concrete (RC) beams, in which the concrete heterogeneities and the nonlinear concrete-steel interaction were taken into account. The developed meso-scale simulation method was then validated by comparing the simulation results with the available tests for RC cantilever beams. In addition, the effects of stirrups ratio, shear-span ratio and loading mode on the size effect in shear strength of RC beams with a maximum depth of 2 000 mm were explored. The simulation results indicate that:1) The shear strength of beams without web reinforcement presents obvious size effect, and the influence coefficient of section height proposed by Chinese Code for design of concrete structures cannot fully reflect the size effect of RC beams; 2) The web reinforcements can inhibit size effect on the shear strength of RC beams, and the size effect on shear strength of beams gradually weakens with the increase of stirrups ratio; 3) As the shear-span ratio increases, the shear capacity of the beam decreases, and the size effect becomes to be weakened; 4) Compared with monotonic loading, cyclic loading leads to the low-cyclic fatigue failure of RC beams, and thus it makes the size effect in shear strength more prominent.