The design and operation of greenhouse structures suitable for specific climate conditions is critical, especially when greenhouse cooling is expected to depend entirely on natural ventilation. The ultimate goal of this study was to investigate the potential enhancement of overall ventilation rates by optimizing greenhouse design parameters such as the area of inlet and outlet vents as well as the type of the insect screen utilized and its area. The Computational Fluid Dynamics (CFD) approach was used, verified by experimental data. Numerical simulations showed that the area of the ventilation openings has a significant effect on the air exchange rate, which increased about 25% when the vent area was enlarged from 6 to 15% of the greenhouse ground area. Another potential design change, the removal of the insect screen from the roof vents, increased the ventilation rates by 25% as compared to the current design. Enlarging the area of the insect screen on the side walls showed no significant improvement in ventilation.