Objective: To investigate the effect of aerobic exercise on pressure overload-induced myocardial remodeling and its mechanism. Methods: Male C57BL/6J mice aged 6-8 weeks were randomly allocated into sham+control (Sham+CON) group, sham+swimming (Sham+SWIM) group, TAC+control (TAC+CON) group, and TAC+swimming (TAC+SWIM) group. One week after operation, mice in the swimming groups commenced aerobic exercise training. After the aerobic training, echocardiography was employed to assess the cardiac function of the mice, while HE staining, Masson staining, and TUNEL staining were utilized to examine and analyze the cross-sectional area of myocardial cells, myocardial interstitial fibrosis, and apoptosis of myocardial cells. The protein expression levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Collagen I and III,Bax, Bcl-2, phosphorylated transforming growth factor-β-activated kinase 1 (p-TAK1), phosphorylated c-Jun N-terminal kinase 1/2 (p-JNK1/2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated P38 (p-P38) were investigated through western blot analysis. Results: Echocardiographic assessment revealed that the TAC+CON group had significantly lower left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) (all P<0.05), compared with the Sham+CON group. Aerobic exercise could significantly improve the LVFS and LVEF of TAC mice. Hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and TUNEL staining demonstrated that aerobic exercise notably diminished the cross-sectional area of cardiomyocytes, myocardial interstitial fibrosis, and cardiomyocyte apoptosis in TAC mice (all P<0.05). Western blot analysis indicated that compared with the Sham+CON group, protein expression levels of ANP, BNP, Bax, Collagen I and Collagen III were increased, Bcl-2 expression was decreased, and the  phosphorylation levels of TAK1, JNK1/2, ERK1/2, and P38 proteins were elevated in the TAC+CON group (all P<0.05). After aerobic exercise, protein expression levels of ANP, BNP, Bax, Collagen I and Collagen III were decreased, Bcl-2 expression was increased, and phosphorylation levels of TAK1, JNK1/2, ERK1/2, and P38 proteins were decreased (all P<0.05). Conclusion: Aerobic exercise can enhance cardiac function in TAC mice by suppressing the TAK1-MAPK signaling pathway, thus ameliorating myocardial interstitial fibrosis and mitigating pressure overload-induced cardiomyocyte apoptosis.