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Given the major role that oxidants play in cellular damage, and the recent focus on antioxidants as treatment for muscle injuries, the aim of this study was to examine the effect of short-term postinjury grape seed–derived polyphenol supplementation on muscle inflammation and repair processes after contusion injury.Experimental injury of the right gastrocnemius muscle was achieved by drop-mass method (200 g from a height of 50 cm), after which rats were gavaged with either 0.9% saline (placebo—PLA) or 20 mg·kg−1·d−1 of proanthocyanidolic oligomer (PCO) from 2 h after contusion injury, for up to 14 d after injury. Blood samples and injured muscle were collected at 4 h and at days 1, 3, 5, 7, and 14 after injury.Compared to an uninjured control group, PCO supplementation resulted in an earlier peak in number of activated satellite cells in contusion-injured muscle tissue (4 h for PCO vs day 3 for PLA, n = 4 per time point per group) and fetal myosin heavy chain expression (day 5 for PCO, P < 0.01 with no change in PLA, n = 3 per time point per group), indicative of quicker muscle regeneration. PCO supplementation limited neutrophil infiltration and facilitated earlier macrophage infiltration into the injured area (n = 4 per group). PCO also resulted in an earlier return toward control levels of muscle proinflammatory cytokines on day 3 (P < 0.01 for interleukin 6 and P < 0 05 for tumor necrosis factor α, both n = 3 per group).Data show that short-term postinjury PCO supplementation was able to quicken muscle regeneration by facilitating earlier recruitment of activated satellite cells and to modulate the immune system in favor of an anti-inflammatory status.