Angiotensin II (Ang II) has a clear role in development of cardiac hypertrophy, fibrosis and dysfunction. It has been difficult, however, to determine whether these actions are direct or consequences of its systemic hemodynamic effects in vivo. To overcome this limitation, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases Ang II from cardiomyocytes (Tg-Ang II-cardiac) without involvement of the systemic renin-angiotensin system and tested whether increased cardiac Ang II accelerates remodeling and dysfunction post-myocardial infarction (MI), while those mice show no evidence of cardiac hypertrophy under the basal condition. Male 12-14-week-old Tg-Ang II-cardiac mice and their wild-type littermates (WT) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 8 weeks. Cardiac Ang II levels were about 10-fold higher in Tg-Ang II-cardiac mice than their WT, whereas Ang II levels in plasma and other tissues did not differ between strains. Systolic blood pressure and heart rate were similar between groups with or without MI. In sham-MI, Tg-Ang II-cardiac mice had increased collagen deposition and decreased capillary density. The differences between strains became more pronounced after MI. Although cardiac function was well preserved in the Tg-Ang II-cardiac mice with sham-MI, cardiac remodeling and dysfunction post-MI were more severe than WT. Our results demonstrate that independent of systemic hemodynamic effects, cardiac Ang II may act locally in the heart, causing interstitial fibrosis in sham-MI and accelerating deterioration of cardiac dysfunction and remodeling post-MI.