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Eccentric exercise has been extensively used as a model to study the contraction-induced muscle damage and its consequent processes. This study aimed at examining molecular responses associated with tissue remodelling, inflammation and angiogenesis in skeletal muscle during the recovery period after eccentric exercise in humans. Ten healthy men performed 50 maximal eccentric muscle actions with the knee extensors and muscle biopsies were collected from the vastus lateralis before and 6 h, 48 h and 120 h post eccentric exercise. Real Time-PCR was utilized to investigate alterations in gene expression of various tissue remodelling-, inflammation- and angiogenesis-related factors: uPA, uPA-R, TGF-β1, MMP-9, TNF-α, IL-6, IL-8, VEGF, VEGFR-2, HIF-1a, Ang-1, Ang-2 and Tie-2. The uPA/uPA-R system exhibited a similar time-expression pattern increasing 6 h post exercise (p < 0.05), while the other tissue remodelling factors TGF-β1 and MMP-9 did not change significantly over time. Transcriptional responses of inflammatory factors TNF-α and IL-8 increased significantly and peaked 6 h post eccentric exercise (p < 0.05), while IL-6 exhibited a similar, though not statistically significant, expression profile (p > 0.05). Similarly, the expression of angiopoietin receptor Tie-2 showed an early increase only at 6 h after the completion of exercise (p < 0.05), while the other angiogenic factors failed to reach statistical significance due a high interindividual variability in the gene expression responses. The early transcriptional upregulation of tissue remodelling, inflammation- and angiogenesis-related factors post eccentric exercise may indicate the acute intramuscular activation of these processes functionally related to muscle damage-induced adaptation.