Our identification of the PI3K/STAT3 pathway as a necessary regulator of the macrophage phenotypes provides new insights into how fibroblasts transdifferentiated into myofibroblasts that contribute cardiac collagen deposition and fibrosis formation after MI n‐butylidenephthalide inhibits ageing‐ and MI‐induced activation of cardiac fibroblasts through a PI3K/STAT3‐dependent mechanism, suggesting that strategies to activate the PI3K/STAT3 pathway may represent a novel and efficacious treatment for MI. This evidence concerns the gene STAT3 and myocardial infarction.