Despite evidence that increased age negatively impacts the functional and physiological recovery of soft tissue following traumatic musculoskeletal injury, there is no consensus as to the mechanism(s) at the molecular/cellular level by which this takes place. PURPOSE: To investigate if there is an age-dependent differential responsiveness to chemokine proteins following stretch-shortening contraction (SSC)- induced musculoskeletal injury. METHODS: Using an in vivo rodent dynamometry model and an NIA-approved animal model of aging (Fisher 344 x Brown Norway Rat), we exposed young and old rats acutely to either zero (0) SSCs or 150 injurious SSCs and assessed multiple chemokine protein responses in tibialis anterior muscle at three days recovery in these populations (n = 8 rats/group). Two-way ANOVA was used for statistical analysis; significance was set at p < 0.05. RESULTS: Following in vivo SSC-injury loading, young rats exhibited increased concentrations of the chemokine proteins RANTES/CCL5 approximately 5 Fold (164.2 + 21.5 vs. 31.1 + 7.6 pg/ml, p < 0.01), GROKC/ CXCL2 approximately 13 Fold (157.6 + 42.1 vs. 11.2 + 3.0 pg/ml, p < 0.001), MCP-1/CCL2 approximately 48 Fold (2,920.6 + 844.0 vs. 60.2 + 10.3 pg./ml, p < 0.0001), and MIP-1alpha approximately 31 Fold (220.5 + 65.6 vs. 7.2 + 1.2 pg/ml p < 0.0001), whereas no such change was observed in old rats. Further, when normalized to old rats, young rats' chemokine protein concentrations were higher for GRO-KC/CXCL2 approximately 5 Fold (157.6 + 42.1 vs. 29.2 + 11.2 pg/ml, p < 0.001), MCP-1/CCL2 approximately 12 Fold (2,920.6 + 844.0 vs. 235.4 + 46.7 pg/ ml, p < 0.0001), and MIP-1alpha approximately 19 Fold (220.5 + 65.6 vs. 11.3 + 2.3 pg/ml, p < 0.0001). CONCLUSIONS: These in vivo data reveal that specific inflammatory mediators, specifically chemokines, in young rats may contribute to a positive healing response following SSC-injury loading; and, actually may become desensitized with increased age. These data may help contribute to explaining the delayed recovery kinetics at the functional level observed with aged populations following traumatic musculoskeletal injury.