Objective Single mechanical ventilation for curing severe acute respiratory distress syndrome (ARDS) is sometimes not effective in improving oxygenation and removing excess CO₂ in the blood. The purpose of this study is to observe the effect of continuous renal replacement therapy（CRRT）combined with low-flow extracorporeal membrane oxygenation （ECMO）of V-V mode on clearance of inflammatory mediators，improving oxygenation and reducing PaCO₂ in canines with ARDS and hypercapnia. Methods 30 healthy adult canines were divided into 3 groups (n=10 each) using a random number table method sham group, ECMO (EC) group and CRRT+ECMO（CR+EC）group. A canine model of ARDS with hypercapnia were prepared by injected intravenously oleic acid. Sham group was only treated with invasive mechanical ventilation. EC group was treated with invasive mechanical ventilation and ECMO. CR+EC group was treated with CRRT combined with low-flow ECMO of V-V mode besides invasive mechanical ventilation. The heart rate(HR)，mean artery pressure (MAP)，cardiac output(CO) and concentration of serum TNF-α and IL-6 were examined at the beginning of modeling(T₀)，after 1，3，6 and 9 (T₁, T₃, T₆, T₉) hours of mechanical treatment respectively. Oxygenation index（OI），PaCO₂, temperature（T）were examined at the beginning of modeling，after 3, 6, 9 hours of mechanical treatment，and at the time point of 3 hours(T12) after ECMO treatment (EC group) and CRRT+ECMO treatment(CR+EC group)，respectively. The differences were compared between groups involved in above-mentioned indexes at different time points. Results Compared with the sham group, the HR decreased at T₆ and T₉ in the EC group and CR+EC group (P<0.05), and the concentration of IL-6 and TNF-α decreased at T₃, T₆ and T₉ in the CR+EC group (P<0.05). Compared with T₀, HR decreased at T₆ and T₉ in the EC group (P<0.05). Compared with T₀, the concentration of IL-6 and TNF-α decreased at T₃, T₆ and T₉ in the CR+EC group (P<0.05). Compared with the EC group, the HR decreased at T₆ and T₉ in the CR+EC group (P<0.05). Compared with the EC group, the concentration of IL-6 and TNF-α decreased at T₃, T₆ and T₉ in the CR+EC group (P<0.05). Compared with the sham group, the OI decreased at T₉ and T₁₂ in the CR+EC group (P<0.05). Compared with the sham group, PaCO₂ decreased at T₃, T₆ and T₉ in the EC group and CR+EC group (P<0.05). Compared with the EC group, the OI decreased at T₉ and T₁₂ in the CR+EC group (P<0.05). Compared with T₀, the OI decreased at T₆ and T₁₂ in the CR+EC group (P<0.05). Conclusion The CRRT combined with low-flow ECMO of V-V mode has positive effects on clearance of inflammatory mediators，reducing hypercapnia and improving oxygenation in the canines with ARDS and hypercapnia.