Objective To reveal the therapeutic effect and mechanism of grape seed proanthocyanidin extract （GSPE） on sports joint injury （SJI） in rats.Methods After the establishment of the SJI rat model， rats in each group were orally administered different doses of GSPE （0， 50， 100， and 200 mg/kg） for 4 weeks， and a normal control group was established. After the administration of the test substance， the pain condition of the model rats in each group was assessed using the paw withdrawal threshold （PWT） assay. Tail vein blood was collected to detect serum superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） content. After the rats were sacrificed， the knee joints were harvested and stained with safranin O-fast green for pathological examination. The protein expression levels of peroxisome proliferator-activated receptor gamma coactivator alpha （PGC-1α）， phosphorylated-AMP-dependent protein kinase alpha （p-AMPKα）， AMPKα， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM） in knee joint tissue were determined using Western blot.Results With increasing GSPE dose， the PWT of rats with SJI increased （P<0.05）， the shape of knee joint lesions improved， serum SOD and GSH-Px contents increased， and MDA content decreased （P<0.05）. The protein expression levels of PGC-1α， p-AMPKα/AMPKα， NRF-1， and TFAM in knee joint tissues of rats with SJI increased with increasing GSPE dose （P<0.05）.Conclusion GSPE intake effectively alleviated pain and knee joint injury in rats with SJI， and the mechanism was related to the activation of the AMPK/PGC-1α mitochondrial pathway， which inhibits oxidative stress in vivo.