Objectives: Adenosine and adenosine A 1 receptor agonists exert protective effects against reperfusion injury in different tissues by mediating preconditioning. The aim of the present study was to examine the effects of adenosine A 1/A 2 receptor activation on reperfusion-induced small intestinal injury in rat.,Methods: Animals were randomized into four groups each including eight as following: sham control, ischemia-reperfusion control, 5'-N-ethylcarboxamidoadenosine (NECA) (non-selective A 1/A 2 agonist, 0.1 mg/kg, i.v.)-treated I/R, and theophylline (non-selective A 1/A 2 antagonist, 20 mg/kg, i.v.)-treated I/R groups. The treatments were administered 5 min before inducing ischemia in which superior mesenteric artery was clamped for 30 min followed by 180 min of reperfusion period. Myeloperoxidase, malondialdehyde, and reduced glutathione contents of terminal ileum samples were measured besides recording contractile responses to KCl, carbachol and substance P.,Results: Ischemic insult significantly increased neutrophil infiltration and lipid peroxidation while decreasing the reduced glutathione. Contractile responses were seriously reduced in I/R group compared to that of the sham control group. NECA pretreatment alleviated the tissue content of reduced glutathione remarkably besides providing partial amelioration of I/R-reduced contractile response, while theophylline pretreatment had no any protective effect.,Conclusion: We offer additional evidence that activation of A 1/A 2 adenosine receptors provides partial protection against ischemia-induced intestinal contractile dysfunction possibly through maintaining reduced glutathione content at physiological levels.