We tested hypothesis that acute myocardial infarction (AMI) induces cellular apoptosis and serial changes of protein kinase C epsilon (PKC-ε) and p38 mitogen-activated protein kinase (p38 MAPK), and tested cardioprotective effect of losartan in this condition. The rats were assigned to group A (sacrificed on day 2), group B (sacrificed on day 5), and group C (sacrificed on day 14). Rats in each group were further randomized into the following groups: AMI (ligation of left coronary artery) without losartan (AMI-L0); AMI with losartan 20 mg/kg/d (AMI-L1); and sham groups (L0 and L1). The PKC-ε expression in membrane compartment was increased in AMI-L1 group than in other groups on day 5 and in AMI groups than in sham groups on day 14 (P < .01). Phosphorylated form of cytosolic p38 MAPK level was increased in AMI-L1 than in other groups on day 14 (P < .05). Furthermore, 14-day left ventricular ejection fraction was higher and cellular apoptosis was lower in AMI-L1 group than in AMI-L0 group (P < .0001).