Mitral regurgitation (MR) is a widely prevalent heart valve lesion that initiates cardiac remodeling over a period of time until failure. While uncorrected MR is associated with greater risks of adverse cardiac events, the current knowledge of the underlying mechanisms in the disease progression remain incomplete. To understand the molecular mechanisms that contribute to let ventricular adverse remodeling, animal models have been described. Small animal models of volume overload induced cardiac remodeling have been reported and widely used, with the aorto-caval fistula model being the most commonly used model to study volume overload. However, this model does not accurately represent the low-pressure volume overload that is seen clinically in patients with primary MR. Here, we describe a rodent model of severe volume overload induced MR in which the mitral leaflet is perforated with a 23 G needle in the beating heart with echocardiographic image guidance. The severity of MR is assessed with echocardiography and is reproducible. This feasible model can be used to study longitudinal changes to the left ventricle.