We have previously shown that adenosine (Ado) restores angiotensin II (Ang II) contractions of isolated perfused afferent arterioles by intracellular mechanisms increasing calcium sensitivity of the contractile apparatus. In the present study we investigated the contribution of p38 MAPK and MK2 to the Ado effect. Mouse mesenteric arteries were studied in the isometric preparation. Ado incubation resulted in the restoration of the desensitised consecutive contractions to Ang II and in the significant increase of the dose-dependent Ang II contractility. Moreover Ado incubation resulted in an enhanced phosphorylation of MLC20 and p38 MAPK and in a significant increase of the calcium sensitivity. Use of specific p38 MAPK inhibitor and MK2-/- mice reversed the Ado effects on both the phosphorylation of MLC20 and Ang II contractility. These effects of Ado are intracellular and receptor independent, since the use of specific nucleoside transporters prevented the restoration of Ang II contractions and inhibition of Ado receptors did not. In conclusion, we show that Ado increases Ang II contractility by mechanisms including activation of p38 MAPK/MK2 pathway increasing sensitivity of the contractile apparatus to calcium.