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We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4\u20136 L\/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8\u201310 L\/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology, and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L\/min, which was associated with enrichment of acute inflammatory and innate responses. 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