Abstract: The volume overload animal models can be divided into low pressure and high pressure models. Mitral regurgitation is often used in low pressure models, whereas aortic regurgitation and aortocaval fistula are often used in high pressure models. Volume overload is related to extracellular matrix (ECM) and might cause left ventricular ECM remodeling, inducing progressively structural and functional left ventricular remodeling and ECM degradation and turnover imbalance. Mast cell, cardiac fibroblast, and reactive oxygen species play important roles in the process of volume overload in heart failure. In this review, the difference between the mechanisms of volume overload and pressure overload in heart failure, and the difference between hypertrophy-related signals in these two kinds of overload cardiac remodeling were reviewed. The review suggests that the calcineurin (CaN) and protein kinase B (Akt) may become the target in the treatment of volume overload and pressure overload in heart failure. In the future, further studies are needed to unveil the difference in the regulation of upstream and downstream regulatory factors in two kinds of overload cardiac remodeling.