Cardiovascular inflammation has been regarded as a major cause for heart failure. However, the mechanisms that are involved in the regulation of cardiovascular inflammation are not well understood. In this chapter, we review the recent progress in revealing the roles of STAT3 in cardiovascular inflammation. Particularly, we discuss cardiomyocyte-specific STAT3-deficient mice and their phenotypes. An emerging view is that STAT3 plays a key role not only in cardiac protection but also in the control of cardiac-related inflammation.