Tracheal gas insufflation (TGI) decreases dead space (V D) and can be combined with continuous positive airway pressure (CPAP) to decrease minute volume (VE) and effort of breathing. In 11 anesthetized sheep, we induced acute lung injury (ALI) through oleic acid (OA) infusion and studied the effects of TGI combined with CPAP (CPAP-TGI) at different TGI flows and with catheters of different designs. Sheep were randomized to two groups: Group A (n = 7) was placed on CPAP and CPAP-TGI at 10 and 15 L/min of insufflation flow delivered through a reverse thrust catheter (RTC). Group B (n = 4) was placed on CPAP and CPAP-TGI at a flow of 10 L/min delivered through a RTC, and through a straight flow catheter (SFC). Compared with CPAP alone, CPAP-TGI resulted in significantly lower VD, VE, pressure time product, and work of breathing. We found no additional benefit from TGI flow of 15 L/min, compared with 10 L/min, and no statistically significant difference between the SFC and the RTC. In conclusion, TGI can be combined with CPAP in this model of ALI to reduce ventilation and effort of breathing.