Background: Carbon dioxide (CO₂) baths have been used to treat a variety of diseases, but developing an artificial bath of highly concentrated CO₂ is difficult. Here, we tried the efficacy of a novel device instead of a CO₂ bath. Methods and Results: Using a device equipped with double fluid nozzles, CO₂ gas and H₂O were compounded and compressed at 4 barometric pressures. As a result, CO₂ gas was dissolved in H₂O, which contained a few micrometers of CO₂ particles, namely, a CO₂ mist. Wistar rats with myocardial infarction (MI) by ligation of the left coronary artery were percutaneously administered CO₂ mist or CO₂ gas alone or no treatment for 30min daily. With regard to tissue blood flow during treatment, the group treated with CO₂ mist had significantly increased tissue oxygenated hemoglobin levels and tissue saturation levels, and significantly decreased deoxygenated hemoglobin levels compared with the group treated with CO₂ gas. After 4 weeks treatment, the group treated with CO₂ mist had a significantly improved ejection fraction by echocardiography compared with the untreated group. Interestingly, the group treated with CO₂ mist had significantly increased nitrate concentrations in serum and vascular endothelial growth factor mRNA expression levels in the myocardium compared with the untreated group. Conclusions: Our new mist production device may be potentially useful for the treatment of heart failure caused by MI. (Circ J 2012; 76: 1203-1212)