MicroRNAs (miRNAs) have been increasingly reported to have important roles in diverse biological and pathological processes. We investigated miR-1 and miR-206 expression and their potential roles in a rat model of myocardial infarction (MI). miR-1 and miR-206 expression were significantly increased, and insulin-like growth factor 1 (IGF-1) protein was markedly reduced without obvious change of its mRNA level after MI induction. Position 175-196 of rat IGF-1 3'-untranslated region was identified to be required for efficient downregulation by miR-1/miR-206. IGF-1 level was reduced without changing its transcript level in rat H9C2 myoblast cells modified with miR-1 (H9C2-miR-1). In the serum withdrawal and hypoxic condition, caspase-3 activity and mitochondrial potential were significantly increased in H9C2-miR-1 cells compared with the control group, respectively (p<0.05, p<0.01). Together, our results indicate that miR-1 and miR-206 are involved in apoptotic cell death in MI by post-transcriptional repression of IGF-1.