This communication deals with the study of new interfacial instabilities, called “grainy” defects, in coextrusion process of reactive multilayer polymers. The main objective has to gain a better understanding of this phenomenon since no help is found in the literature. A fundamental approach is purposed from micro-to macro scale involving the study of polymer structure, processing and interfacial properties relationship. Influence of these parameters on the generation of “grainy” defect in coextrusion has been assessed in correlation with physico-chemical properties. Through this work, rheological properties and morphology of interface between tie and barrier layers have been investigated via shear stress relaxation experiments and transmission electronic miscroscopy (TEM), respectively. Depending on the reactive polymers, interfacial coupling could significantly alter the stress relaxation behavior by extending the relaxation time and also generate interfacial roughening. Hence, relationships between copolymer architecture, relaxation process and interfacial morphology were established in correlation with the generation of grainy defects in coextrusion process.