Thermal Barrier Coatings (TBC) are ceramic layers enabling metallic components to resist to severe operating temperature and prolonging their lifetime. Typically, TBC are composed of a ceramic Top-Coat (TC) for thermal insulation, an intermediate metallic bond-coat (BC) layer located between a superalloy substrate and the TC, and an oxidation-resistant layer called Thermally Grown Oxide (TGO) [1]. Predicting interface delamination and failure of TBC under thermo-mechanical loading is quite complex due to the severity of thermal conditions and the heterogeneity of their structure. Besides, several parameters and phenomena lead to premature TBC failure reducing consequently their operating lifetime. Among these factors, thermal expansion mismatch, oxidation, interface roughness and creep play a major role and must be taken into account for prediction purposes. This work deals with a Discrete Element Method (DEM) to investigate the thermo-mechanical behavior of TBC during a thermal cycle. Originally developed to model granular materials, DEM has been adapted to simulate continuous media using cohesive spring or beam elements. Thus, it has turned into a promising approach to simulate the mechanical or thermo-mechanical behavior of homogeneous and heterogeneous materials. In the present contribution, emphasis is placed on thermo-mechanical stresses arising in TBC during a complete thermal cycle due to combined effects of creep and thermal expansion. The context of a plasma-sprayed ceramic TC and a NiCrAlY BC is studied. In a first step, based on a recent contribution [2], a DEM approach to reproduce creep effets occurring during the dwelling phase at high temperature is proposed and validated. Then, effects of roughness and thickness of TGO layer are discussed considering a unit cell in which the TBC interface has a sinusoidal profile. Finally, the case of a realistic TBC sample model built by image processing is investigated. Such a model takes into account defects as pre-existent pores and cracks and an irregular TBC interface.