The previous study revealed that a nanobubble generator using honeycomb structures may produce a large amount of water including large nanobubble density in a short time. In this paper, numerical simulations are performed for bubbly flow in the honeycomb structure by applying a computational fluid dynamics (CFD) coupled with a population balance model (PBM). The numerical model is based on the Eulerian multiphase model and the PBM was used to calculate the gas bubble size distribution considering the bubble coalescence and breakage. The results show that bubble size distributions in the honeycomb structure under different inlet absolute pressure can be predicted by the PBM. It may be concluded that the maximum shear stress is the main controlling factor for the nanobubble generation.