ckground information: Bone marrow-derived mesenchymal stem cells (MSCs) reduce acute lung injury in animals challenged by bleomycin or bacterial lipopolysaccaride. It is not known, however, whether MSCs protect from ventilator- induced lung injury (VILI). Question of the study: Whether MSCs have a potential role in preventing or modulating VILI in healthy rats subjected to high-volume ventilation. Materials and methods: 24 Sprague-Dawley rats (250-300 g) were subjected to high- volume mechanical ventilation (25 ml/kg). MSCs (5x106) were intravenously or intratracheally administered (N=8 each) 30 min before starting over-ventilation and 8 rats were MSC-untreated. Spontaneously breathing anesthetised rats (N=8) served as controls. After 3 h of over-ventilation/control the animals were sacrificed and lung tissue and bronchoalveolar lavage fluid (BALF) were sampled for further analysis. Results: When compared with controls, MSC-untreated over-ventilated rats exhibited typical VILI features. Lung edema histological lung injury index, concentrations of total protein, interleukin-1β, macrophage inflammatory protein-2 and number of neutrophils in BALF and vascular cell adhesion protein-1 in lung tissue significantly increased in overventilated rats. All these indices of VILI moved significantly towards normalization in the rats treated with MSCs, whether intravenously or intratracheally. Answer to question: Both local and systemic pre-treatment with MSCs reduced VILI in a rat model.