Compared to healthy age-matched controls (HC), patients with COPD have impaired muscle metabolism and function, which contributes to exercise intolerance. We aimed to determine whether the temporal transcriptional response of muscle to endurance exercise training in COPD was different to HC, and if so whether any differences could be associated with the magnitude of physiological training adaptation (VO2PEAK). Nineteen patients with COPD and 10 HC (Table 1), none of whom exercised regularly, performed symptom limited incremental cycle ergometry, lean mass assessment (DEXA), physical activity monitoring (tri-axial accelerometery) and underwent resting (fasted state) vastus lateralis muscle biopsies at baseline and after 1, 4 and 8 weeks of supervised cycle exercise training (30 min 65% peak power, 3 x week). mRNA was extracted from vastus lateralis tissue and the expression of 94 genes, selected because of their known responsiveness to exercise intervention, was assessed using quantitative RT-PCR. Gene expression data were analysed using Ingenuity Pathway Analysis (IPA; Qiagen) to identify significantly changed biological functions. Altered biological functions were apparent at weeks 1, 4 and 8 in both groups (Figure 1). A similar response was observed in both groups for networks representing energy production and fuel selection; muscle and connective tissue development and function; and free radical scavenging and inflammation. VO2PEAK increased 15% in the HC group (p < 0.01) but was unaltered in the COPD group (p = 0.62) following training. Both HC and COPD groups experienced similar temporal transcriptional responses to endurance exercise training. Furthermore, functions of gene networks found to be significantly altered were similar. Changes in mRNA expression were not however associated with increases in whole-body VO2PEAK in response to training, with COPD patients showing a clear transcriptional response, but no increase in VO2PEAK. These data support the contention that the responsiveness of skeletal muscle to exercise training in COPD is not blunted, at least at the level of mRNA expression.