Acute respiratory distress syndrome (ARDS) is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6 hour pilot study, we analyzed the use of the combination of both stem cell and extracorporeal membrane oxygenation (ECMO) strategies to prevent or treat severe lung injury. A total of 11 sheep were used. Five sheep received Escherichia coli endotoxin as a control group (group 1). Three sheep that received E. coli endotoxin were treated with veno-venous ECMO support in group 2. In group 3, 3 sheep received a dose of clinical grade good manufacturing practice (GMP)-produced MultiPotent Adult Progenitor cells (MAPC) intratracheally after the end of the infusion of E. coli endotoxin, followed by ECMO support. The respiratory parameters by means of blood gas results, measurements of lung injury, inflammatory responses, and integrity of the alveolar capillary barrier after the infusion of these cells were analyzed. Our data suggest that the combination of ECMO and stem cell therapy showed better histopathologic changes with less inflammation. We believe that the combination of stem cells with the ECMO treatment may be useful in future studies investigating the diagnosis, treatment, and prevention of ARDS.