Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Male C57/BL6 mice were used to establish the MI model and were divided into three groups: sedentary MI group (MI), MI with aerobic exercise group, and MI with resistance exercise group; sham-operated group was used as control. Exercise-trained animals were subjected to 4 wk of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis, and degradation and apoptosis in gastrocnemius muscle were detected. H O -treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1 receptor (IGF-1R) inhibitor NVP-AEW541, and PI3K inhibitor LY294002 to explore the mechanism. Exercises upregulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling; increased the expressions of Pax7, myogenic regulatory factors (MRFs), and protein synthesis; and reduced protein degradation and cell apoptosis in MI mice. In vitro, IGF-1 upregulated the levels of Pax7, MRFs, mTOR, and P70S6K; reduced MuRF1 and MAFbx; and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation, and cell apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt signaling pathway.