Objective To study the effect of sea cucumber peptide on mitochondrial function of skeletal muscle in exercise-induced fatigue rats. Methods Fifty male rats were divided into five groups; the control group, model group and low-dose, medium-dose, and high-dosesea cucumber peptide groups. Except for the control group, the exercise-induced fatigue rat models were established by exhaustive swimming method for weight-bearing swimming training. Rats in the low-dose, medium-dose, and high-dose sea cucumber peptide groups were administrated 300, 150, and 75 mg/kg sea cucumber peptide,respectively. The rats in the control and model groups were given the same volume of purified water. They were all treated for 28 days. At the end of study, we killed the rats to obtain the quadriceps femoris tissues, file skeletal muscle level of super oxide dismutase (SOD), malonie aldehyde (MDA) and glutathione peroxidase (GPx) were detected by spectrophotometry. Moreover, mitochondrial permeability transition pore (Pl’P), mitochondrial respiratory chain complexes I and III were determined. Die expression levels of mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1-a(PGC-lα) and estrogen-related receptor (ERR) were detected using Western blotting. Results Compared with the control group, the SOD and GPx activities decreased and the MDA level increased (P <0.05 or P <0.01) ;the mitochondrial PTPopenness increased (P <0.01), the mitochondrial respiratory chain complexes I and III decreased (both P < 0.01), and the expression of mitochondrial PGC-la and ERR decreased in the model group (P <0.05 or P <0.01). Compared with the model group, SOD and GPx activities in skeletal muscle tissues increased, and MDA content decreased (P <0.05 or P < 0.01) ; the skeletal muscle mitochondrial PTP openness decreased (P < 0.01), the mitochondrial respiratory chain complexes I and III increased (P < 0.05 or P <0.01), and the expression of mitochondrial PGC-lα and ERR increased in the low-dose, medium-dose, and high-dose sea cucumber peptide groups(P < 0.05 or P <0.01). Conclusion Sea cucumber peptide ameliorates exercise-induced fatigue in rats, decreases skeletal muscle mitochondrial swelling and mitochondrial membrane permeability, enhances mitochondrial respiratory function, and up-regulates mitochondrial PGC-la and ERR expression. [ABSTRACT FROM AUTHOR]