['The coupling and timing of pro- and anti-inflammatory processes in skeletal muscle injury is poorly understood. We investigated the temporal response and regulated processes of extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and IkappaB kinase (IKK) α/β signaling pathways after traumatic injury.', 'Traumatic freeze injury was delivered to the tibialis anterior (TA) muscle in C57BL/6J mice, and injured and uninjured TA muscles were analyzed 3-72 h into the recovery period.', 'Significant increases in pro-inflammatory cytokine transcription accompanied IKKβ phosphorylation, robust ERK pathway activation, and reduced heat shock protein (Hsp) protein expression at 3-24 h. At 24 h, ERK activation was abolished concomitantly with a significant increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). After 24 h, cytokine transcription along with ERK1/2 and IKKβ phosphorylation remained suppressed, whereas Hsp protein expression rose to significant levels by 72 h and associated with IKKβ.'] Does time-course analysis of injured skeletal muscle suggest a critical involvement of ERK1/2 signaling in the acute inflammatory response?