Abstract Previous studies have demonstrated that acute lung injury (ALI) is associated with significant mortality and so far no effective pharmacotherapy is shown to reverse the natural progression. This study aims to investigate whether the transplantation of bone marrow derived mesenchymal stem cells (MSCs) might restore damaged pulmonary function and tissue structure in ALI. By using a sublethal chest impact injury plus endotoxemia model, MSCs were intravenously transplanted into the injured rats 2h after trauma. The blood samples were obtained for determination of blood gas. Bronchoalveolar lavage fluid (BALF) was collected for analysis of inflammatory cell count and cytokine (TNF-α, IL-1β, IL-6 and IL-10) levels. The left lower lobes of the lungs, nearby the impact zone, were collected for SRY gene analysis and histological examination and scoring. After engraftment of MSCs, the number of inflammatory cells in BALF was decreased. Meanwhile, the secretions of pro-inflammatory TNF-α and IL-6 were alleviated, while the secretion of anti-inflammatory IL-10 was elevated. Engraftment of MSCs improved the pulmonary gas exchanges, alleviated the lung injury, and reduced the rats' mortality. These results suggested that the MSCs based measures might be a promising strategy in trauma and endotoxemia induced ALI treatment.