Introduction: Allopurinol acts protectively in the ischemia reperfusion injury of the small intestine. The aim of this experimental study is to define the ideal time of administration of allopurinol, in experimental models of ischemia/reperfusion. Materials and Methods: We used 46 rabbits that were divided into four groups. Group A was the control. In Group B allopurinol was administered 10 min before ischemia and in Group C 2 min before reperfusion. In Group D, allopurinol was administered before ischemia and before reperfusion in half doses. Blood samples were collected at three different moments: (t 1 ) prior to ischemia, (t 2 ) prior to reperfusion, and (t 3 ) after the end of the reperfusion, in order to determine superoxide dismutase (SOD) and neopterin values. Specimens of the intestine were obtained for histological analysis and determination of malondialdehyde (MDA). Results: In Group A, mucosal lesions were more extensive compared to those of the other three groups. Similarly, MDA, SOD and neopterin values were significantly higher. On the contrary, Group D showed the mildest mucosal lesions, as well as the lowest MDA, SOD and neopterin values. Finally, the lesions and the above mentioned values were bigger in Group C than in Group D. Conclusions: The administration of allopurinol attenuates the production and damage effect of free oxygen radicals during ischemia reperfusion of the small intestine, thus protecting the intestinal mucosa. Its maximum beneficial action is achieved when administered both before ischemia and before reperfusion of the small intestine.