Morphology evolution of immiscible polymer blends during processing is a common phenomenon, but how it affects the foaming behavior is still unknown. The present work aims to study the effect of morphology evolution of polystyrene/poly(methyl methacrylate) (PS/PMMA) blends driven by phase separation on foaming behavior via a batch foaming process. Morphology evolution of PS/PMMA blends were conducted via thermal annealing using a compression molding machine. Phase contrast optical microscope and scanning electron microscope were used to investigate the morphology evolution and cell structures. The diffusion coefficients were calculated to study the effect of morphology evolution on gas diffusion behavior. It was found that phase domain was increased in size with the annealing and that cell structure was significantly dependent on morphology evolution. The thermal annealing with a long time could dramatically impact cell structures, especially for the blends with a bi-continuous phase structure or a sea-island structure with very large phase domains. The diffusion coefficient for the interface was increased with the annealing, which resulted in the generally decreased expansion ratio. Therefore, annealing for a long time at melt states during processing should be avoided for obtaining welldefined cell structures for immiscible polymer blends.