Since diabetes and myocardial infarction (MI) are associated with an up-regulation of the renin-angiotensin system (RAS), we hypothesized that Angiotensin-II receptor blockers will be beneficial in the peri- and post-large-MI periods, in Wistar and insulin-resistant rats (ZFR).These results indicate that the peri- and post-MI blockade of the RAS reduces arrhythmias and improves peri-MI survival only in the ZFR, while the chronic treatment improved the 24hour-38day survival, ventricular function and remodeling, fetal-gene and GLUT-4 mRNA expression in normal animals.In Wistar rats, Losartan at a high-dose (30mg/kg/day) caused significant hypotension resulting in increased 24hour mortality. In the 24hour post-MI survivors, Losartan administered progressively (3mg/kg/day progressively increased to 30mg/kg/day), reduced mortality between day-1 and day-38, improved ventricular remodeling, hemodynamics and fetal-gene expression profiles. In ZFR, Losartan administered progressively reduced early ventricular arrhythmias resulting in improved survival. Chronically, Losartan reduced cardiac hypertrophy and fetal-gene re-expression, however it did not improve ventricular remodeling and hemodynamics.