© 2016, Springer-Verlag Wien.Background: Acute mesenteric ischemia is a life-threatening clinical entity. 2‑Aminoethoxydiphenyl borate (2-APB) is a membrane-permeable modulator of intracellular inositol triphosphate-induced calcium release. We investigated the effects of different 2‑APB doses on intestinal ischemia-reperfusion injury in an experimental rat model. Methods: We divided 24 Wistar albino rats into four groups: sham, control, ischemia-reperfusion +2 mg/kg 2‑APB, and ischemia-reperfusion +4 mg/kg 2‑APB. The sham group only underwent laparotomy for 1 h 30 min. A 30-min period of mesenteric ischemia was induced in the control and two treatment groups, followed by 1 h of reperfusion. Before the laparotomy, 2 mg/kg and 4 mg/kg 2‑APB was administered i.v. in the treatments groups, and blood samples were collected after reperfusion. Serum levels of malondialdehyde, superoxide dismutase, glutathione, total antioxidant capacity, tumor necrosis factor (TNF)-α, and interleukin-6 were analyzed. Intestinal tissues were taken for histopathological, DNA fragmentation, and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses to determine the proportion of apoptotic cells. Results: 2-APB reduced serum malondialdehyde, TNF-α, and interleukin-6 levels. However, superoxide dismutase and total antioxidant capacity levels increased significantly in the 4‑mg/kg 2‑APB group (p < 0.05). The intestinal histopathological injury scores were significantly higher in the control group; these injuries were prevented in the 4‑mg/kg 2‑APB dose group. DNA damage after ischemia-perfusion decreased significantly in the 4‑mg/kg 2‑APB group compared with the control group. Conclusion: 2-APB decreases oxidative stress and cell injury. Administering 4 mg/kg 2‑APB prevented ischemia-perfusion injury by diminishing histological damage.