Chronic heart failure (HF) is associated with increased systemic (plasma) and reduced local (myocardial) adenosine levels. The final biological action of adenosine in a particular organ or cell population may depend on the relative degree of expression and signaling efficiency of individual adenosine receptor (AR) subtypes. The aim of this study was to determine the myocardial expression of ARs, in the different chambers of failing versus normal minipig hearts. Cardiac tissue was collected from minipigs without (n = 5) and with HF (n = 5). ARs, adenosine deaminase, and tumor necrosis factor-α (TNF-α) mRNA expression were evaluated by real time-polymerase chain reaction. ARs were expressed in all cardiac regions. After 3 weeks of pacing, the only significant change was observed in A2BR mRNA expression in the left ventricle (P = 0.02), with a similar trend for A3R, A2AR, and A1R. A trend toward higher expression of mRNA adenosine deaminase in the myocardium of pigs with HF was observed. TNF-α mRNA expression was higher after HF in all cardiac chambers (left ventricle: P = 0.009), and a significant correlation was observed between TNF-α and A2BR (r = 0.80, P < 0.0001). In this study, A2BR mRNA resulted in being overexpressed in the left ventricle of pigs with HF as well as TNF-α expression possibly testifying a link between AR expression, inflammation, and HF.