Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation. This study investigated whether rehabilitative exercise training decreases the levels of systemic or local muscle inflammation or reverses the abnormalities associated with muscle deconditioning. Methods: Fifteen patients with COPD (mean (SE) forced expiratory volume in 1 s 36 (4)% predicted) undertook high-intensity exercise training 3 days/week for 10 weeks. Before and after the training programme the concentration of tumour necrosis factor a (TNFα), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma was determined by ELISA, and vastus lateralis mRNA expression of TNFα, IL-6, total insulin-like growth factor-I (IGF-I) and its isoform mechanogrowth factor (MGF) and myogenic differentiation factor D (MyoD) were assessed by real-time PCR. Protein levels of TNFα, IGF-I and MyoD were measured by Western blotting. Results: Rehabilitation improved peak exercise work rate by 10 (2%) (p = 0.004) and mean fibre cross-sectional area from 4061 (254) μm2 to 4581 (241) μm2 (p = 0.001). Plasma inflammatory mediators and vastus lateralis expression of TNFα and IL-6 were not significantly modified by training. In contrast, there was a significant increase in mRNA expression of IGF-I (by 67 (22)%; p = 0.044), MGF (by 67 (15)%; p = 0.002) and MyoD (by 116 (30)%; p = 0.001). The increase observed at the mRNA level was also seen at the protein level for IGF-I (by 72 (36)%, p = 0.046) and MyoD (by 67 (21)%; p = 0.012). Conclusions: Pulmonary rehabilitation can induce peripheral muscle adaptations and modifications in factors regulating skeletal muscle hypertrophy and regeneration without decreasing the levels of systemic or local muscle inflammation.