The mucosal folding is a phenomenon observed for some biological tissues, including the pulmonary airway and gastrointestinal tract. In order to understand the mechanism of the formation of mucosal folding, a thick-walled two-layered cylindrical mathematical model was developed to investigate the buckling behavior under the external pressure and circular outer boundary condition. With the finite element method, the validity and accuracy of the proposed model was verified. The results showed that the fold number was in the range of 4-6, which was agreed with the experimental observation for the mucosal folding of a porcine esophagus. The fold number was found to decrease with the increase in the ratio of the inner to outer material stiffness. The increase in the thickness of inner layer also caused a slight declination of the fold number. Since the effects of both the material and geometrical nonlinearities have been accounted for, this model is more general to be used for the prediction of the buckling behavior of the layered structure with a wide range of thickness ratios and/or stiffness ratios.