Postoperative pain following Root Canal Therapy (RCT) is the common problem for patients,dentist and dental staff. Regardless of cause it appears that postoperative pain and discomfort is related to periapical inflammation. The purpose of this study was to investigate histologically the effect of Ibuprofen on acute apical inflammation following RCT. on cat. Fifty-six cuspids teeth of 14 cats were divided into three groups, 6 cats for experimental group, 6 cats for positive control group and 2 cats for negative control group. In first group, to anesthesize the animals each cat received 10 mg/kg Ibuprofen 36 hours before RCT and repeated every 24 hours. In second group RCT was performed in 24 cat teeth without any prescription. In negative control groups 2 cats, no RCT were done.Following vital perfusion, in interval of 6, 12, 24 hours, samples were post fixed in 10% formalin and five micron sections were prepared, and stained with H&E and studied under the Mann Whitney parameter test. Infilteration of inflamatory cells in 6 hours interval in experimental group was significantly less than two control groups. In 12 hours samples, however, inflammation in experimental group reduced, but it was not significant. In 24 hours samples there was no significant difference between experimental groups and controls. The result of this in-vivo study shows prescription of Ibuprofen before root canal therapy can reduce inflammatory reaction.