Physiological heart development and cardiac function rely on the response of cardiomyocytes to mechanical stress signals during hemodynamic loading and unloading. These stresses manifest themselves via changes in cell structure, contractile function and gene expression. Disruption of this well balanced stress-sensing machinery due to various pathological conditions results in contractile dysfunction, cardiac remodeling and heart failure. In order to study signaling mechanisms involved in the pathogenesis of various manifestations of Cardiovascular Disease (CVD), there is a need for physiologically relevant in-vitro models. To accomplish this goal, we have developed a Microfluidic Cardiac Circulation Model (μCCM) that integrates mechanically loaded cardiomyocytes with fluid flow and a circulation network. ©2009 IEEE.