Based on the recent photographs of microstructures of anacinus a novel 3D computational model for airflow and particle transport and deposition was developed. To model the entireacinar region simultaneously, an approach was proposed to reduce the computational space. The airflow was solved using numerical simulations for the cases of expanding and contracting the asinus wall. The volume change of the lung was imposed based on the normal breathing condition with 15% volumetric expansion ratio. Since the entire acinar region was modeled, realistic pressure type boundary conditions were used and the use of earlier unrealistic boundary conditions was avoided. The simulation results showed that the flow patterns in an acinus with moving walls were significantly different from those for the rigid wall case. Furthermore, due to the asymmetric configuration, the flow patterns were not quite symmetric. It was shown that the ratio of alveolar flow to ductal flow rate controlled the dominant flow regime in each generation. Ratios below 0.005led to recirculation regime where flow separation occurred, while values above this threshold led to flows with radial streamlines. In summary, while the flow in the primary generations was characterized by the formation of recirculation regions in the alveoli, the terminal generations were characterized by radial streamlines which move towards the alveolar wall. Both flow regimes had substantial effects on particle deposition in the acinus.