Adenosine inhibited interleukin (IL)-18 production in lipopolysaccharide (LPS)-stimulated monocytes. The action of adenosine was antagonized by an adenosine A2A-receptor (A2AR) antagonist and was mimicked by an A2AR agonist, suggesting that the stimulation of A2AR may be involved in the actions of adenosine. On the other hand, the stimulation of A1R and A3R inhibited the actions of A2AR stimulation, whereas the stimulation of A2BR had no effect on them. Activation of A2AR is known to increase cyclic adenosine monophosphate (cAMP) levels and to activate protein kinase A (PKA). A PKA inhibitor prevented the actions of A2AR stimulation, indicating that the action mechanism of A2AR stimulation may be via the activation of the cAMP/PKA pathway.