Agonist binding of A2A adenosine receptor (A2AAR) shows protective effects against in-flammatory and immune. Efforts are exerted in understanding the general mechanism and developing A2AAR selectively binding agonists. Using molecular dynamics (MD) simula-tions, we have studied the interactions between A2AAR and its agonist (adenosine), and an-alyzed the induced dynamic behaviors of the receptor. Key residues interacting with adeno-sine are identified: A632.61,I662.64, V843.32, L853.33, T883.36, F1685.29, M1775.38, L2496.51, H2506.52, and N2536.55 interacting with adenosine with affinities larger than 0.5 kcal/mol. Moreover, no interaction between adenosine and L1675.28 is observed, which supports our previous findings that L1675.28 is an antagonist specific binding reside. The dynamic be-haviors of agonist bound A2AAR are found to be different from apo-A2AAR in three typical functional switches: (i) tight “ionic lock” forms in adenosine-A2AAR, but it is in equi-librium between formation and breakage in apo-A2AAR; (ii) the “rotamer toggle switch”, T883.36/F2426.44/W2466.48, adopted different rotameric conformations in adenosine-A2AAR and apo-A2AAR; (iii) adenosine-A2AAR has a flexible intracellular loop 2 (IC2) and ɑ-helical IC3, while apo-A2AAR preferred ɑ-helical IC2 and flexible IC3. Our results indicate that agonist binding induced different conformational rearrangements of these characteristic func-tional switches in adenosine-A2AAR and apo-A2AAR.