Purpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. Methods: This experimental study was conducted on 48 male Wistar albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 mu mol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 mu mol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. Results: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p <.05), and significantly increased antioxidant parameters in the intestinal tissues (p <.05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). Conclusion: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.