Diclofenac Sodium (DS) as one of Non-steroidal Anti-inflammatory Drugs (NSAIDS) is a commonly used and may be used in high or toxic doses by mistake or postoperatively. Consequently, the present study was designed to evaluate the possible protectiverole of Moringa Oleifera (MO) on the experimentally induced microscopical changes of duodenal mucosa of adult rats following administration of different high doses of DS. Forty five rats were divided into the following groups (15 each): Group I was served as a control group, Group II was subgrouped to IIa, b and c, that were administered oral 50, 100 and 150 mg/kg of DS respectively for 2 days after fasting for 20 hours. Group III was subgrouped to IIIa, b and c. These rats were maintained on oral MO (500mg/kg) daily for one week, and then they were administered the same doses as in the previous group. A variety of histological changes was observed in group II. The changes were ranged from loss of the brush border to cellular lysis, destruction of villi, monocellular infiltrations and basal glandular ulcerations. The PAS stained sections showed focal negative expression of the brush border together. Although the goblet cells appeared significantly decreased in number, they had increased acidic mucin secretion. In conclusion, the current study suggested that MO may have a limited and partial protective effect on the duodenal mucosa in cases of high dose administration.