Chronic obstructive pulmonary disease (COPD) often causes diaphragm dysfunction, which is the main contributor to neuro-muscular respiratory failure and associated with the prognosis of COPD. However, the morphological changes in diaphragm during the development of COPD are complicated and underlying mechanisms have not been absolutely elucidated. Considering smoking is one of the most leading and important risk factors for development of COPD, we set out to investigate the effects of smoking on muscle fibre remodeling and underlying mechanisms in diaphragms. Rats were randomly exposed to cigarette smoke (CS) for one of three durations of 4, 8, and 12 weeks. CS exposure resulted in increased percentage of type I muscle fibres, enhanced apoptosis index, endoplasmic reticulum (ER) dilation, elevated expression of glucose-regulated protein 78, C/EBP homologous protein, caspase-12, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), cytochrome c oxidase 4, Sdhb, p53 and a reduction in fibre diameters in rat diaphragms. The results indicated that CS exposure induced a shift to muscle fibres with aerobic metabolism in predominance in rat diaphragms, which may be dependent on the regulation of PGC-1α and p53. Additionally, ER stress (ERS) associated apoptosis may contribute to the pathogenesis of diaphragmatic muscle atrophy induced by CS exposure.