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The use of cell therapies has recently increased for the treatment of pulmonary diseases. Mesenchymal stem/stromal cells (MSCs) and alveolar type II cells (ATII) are the main cell-based therapies used for the treatment of acute respiratory distress syndrome (ARDS). Many pre-clinical studies have shown that both therapies generate positive outcomes; however, the differences in the efficiency of MSCs or ATII for reducing lung damage remains to be studied. We compared the potential of both cell therapies, administering them using the same route and dose and equal time points in a sustained acute lung injury (ALI) model. We found that the MSCs and ATII cells have similar therapeutic effects when we tested them in a hydrochloric acid and lipopolysaccharide (HCl-LPS) two-hit ALI model. Both therapies were able to reduce proinflammatory cytokines, decrease neutrophil infiltration, reduce permeability, and moderate hemorrhage and interstitial edema. Although MSCs and ATII cells have been described as targeting different cellular and molecular mechanisms, our data indicates that both cell therapies are successful for the treatment of ALI, with similar beneficial results. Understanding direct cell crosstalk and the factors released from each cell will open the door to more accurate drugs being able to target specific pathways and offer new curative options for ARDS., This work was supported by the Ministerio de Economía y Competitividad– Instituto de Salud Carlos III (PI12/02548 to A.A., and PI12/02451 and PI15/00482 to R.H.), by the Spanish Society of Critical Care (SEMICYUC); we also got funding from Fondo Europeo de Desarrollo Regional (FEDER), Marta Camprubí got a PhD grant by Catalan Society of Pneumology (SOCAP); the CIBER de Enfermedades Respiratorias and a grant from Fundació Parc Taulí obtained by Ferranda Puig supported also this study.