Although it is essential in critical care medicine, mechanical ventilation often results in ventilator‑induced lung injury (VILI). Treating mice with lipopolysaccharide has been reported to upregulate the expression of miR‑127, which has been implicated in the modulation of immune responses. However, the putative roles of miR‑127 during the development of VILI have yet to be elucidated. The present study demonstrated that challenging mice with mechanical ventilation for 6 h significantly upregulated the expression of miR‑127 in bronchoalveolar lavage fluid, serum and lung tissue samples. Conversely, following the downregulation of miR‑127 expression in vivo using an adenovirus delivery system, VILI‑associated pathologies, including alterations in the pulmonary wet/dry ratio, pulmonary permeability, lung neutrophil infiltration and levels of pro‑inflammatory cytokines, were significantly attenuated. In addition, miR‑127 knockdown inhibited the ventilation‑induced activation of nuclear factor (NF)‑κB and p38 mitogen‑activated protein kinase (MAPK). These findings suggested that the upregulation of miR‑127 expression may contribute to the development of VILI, through the modulation of pulmonary permeability, the induction of histopathological alterations, and the potentiation of inflammatory responses involving NF‑κB and p38 MAPK‑associated signaling pathways.