BACKGROUND: In this study, we aimed to examine the therapeutic effects of ozone on the acute phase of intestinal ischemia-reperfusion(I/R) injury in rats to resemble clinical practice.METHODS: Eighteen Wistar albino rats were assigned to control (CG, n=6), sham (SG, n=6) and ozone groups (OG, n=6). A midlinelaparotomy was performed and a superior mesenteric artery (SMA) in the SG and OG was occluded with a 0/0 catgut suture, butin the CG, the incision was closed without any intervention. Tissue oxygenation was monitored with a tissue oxygenation monitorto achieve the same grade during intestinal ischemia. The incision was closed and, in the OG, ozone/oxygen mixture (0.7 mg/kg) wasinjected intraperitoneally, 20 minutes before reperfusion. Surgical incision was reopened and reperfusion was achieved after 60 minutesof ischemia in the SG and OG. After 60 minutes of reperfusion, 2 cm small intestine segment was sampled for histopathologicalassessment of the intestinal mucosal damage (Chiu score) and biochemical assessment of oxidative stress markers (nitric oxide: NO,malondialdehyde: MDA, superoxide dismutase: SOD) in all groups.RESULTS: The Chiu scores of the SG and OG were statistically increased than that of the CG (p=0.002; and p=0.002, respectively).Chiu score in the OG was higher compared to that in the SG, but not statistically significant (p=0.175). MDA levels were statistically higherin the SG and OG than that of the CG (p=0.004; and p=0.010, respectively). However, the difference between the SG and OG was notstatistically significant (p=0.522). SOD and NO levels were not significantly different between groups (p=0.451 and p=0.056, respectively).CONCLUSION: Contrary to the literature, single-dose ozone therapy did not reduce the oxidative stress or improve the ischemicdamage in intestinal I/R injury in rats. Further evaluation with different doses in different time periods is needed for potential clinical use.