Objective: To explore the effects and mechanisms of resveratrol on the improvement of cardiomicronic energy metabolism in exercise-induced fatigue rats. Methods: 48 healthy male SD rats of 6-8 weeks old were selected and randomly divided into blank control group (C), resveratrol administration group (R), exercise-induced fatigue group (E) and exercise-induced fatigue + resveratrol administration group (ER), with 12 rats in each group. The rats in group E and ER were weight-bearing 5% of body weight for 60 min per day and exercised 6 days per week for 6 weeks. Rats in group R and ER were gavaged with resveratrol at 50 mg/kg 1 hr after exercise. Results: Compared with C, E rats showed a significant increase in plasma levels of BUN and CK (P < 0.05, P < 0.05), a significant increase in the activity levels of CK-MB and cTnI (P < 0.01, P < 0.05), a significant decrease in the activity levels of myocardial cytochrome C oxidase (COX) and succinate dehydrogenase (SDH) activity levels were significantly lower (P < 0.01, P < 0.05), and mRNA expression levels of mitochondrial energy metabolism- related genes silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), and estrogen receptor-related receptor α (ERRα) were significantly lower (P < 0.01, P < 0.01, P < 0.01). Compared with E, the serum levels of BUN and CK in ER rats showed a significant decrease (P < 0.05, P < 0.05), the activity levels of CK-MB and cTnI showed a significant decrease (P < 0.05, P < 0.05), the activity levels of myocardial COX and SDH showed a significant increase (P < 0.01, P < 0.05), and the SIRT1, PGC-1α and ERRα expression levels of mRNA were significantly increased (P < 0.05, P < 0.01, P < 0.01). Conclusion: Resveratrol can effectively activate the SIRT1/PGC-1α/ERRα signaling pathway, improve myocardial energy metabolism in exercise fatigued rats, and protect against myocardial injury.