Abstract: The study aimed to assess histology of rat kidneys and explore the renal oxidative stress post treatment with zerumbone via evaluation of some renal metabolizing enzymes and assay of prostaglandin E2 in the serum. To conduct such research, fifty adult male Sprague Dawley rats were randomly assigned into five equal groups. Rats in the first and second groups were administered 2 mL kg–1 body weight of 0.2 and 0.4% w/v zerumbone, respectively. Third group were treated with Celecoxib and served as positive control and rats in the fourth group were received corn oil and served as negative control whereas rats of the fifth group were left without treatment as a basal normal group. Microscopic findings revealed normal picture of the renal tissue and no signs of morphological changes. Biochemical analysis showed that the microsomal content of Cytochrome P450 was significantly induced in the first three groups compared to fourth and fifth groups. Activity of cytosolic glutathione-S-transferase enzyme was induced significantly in zerumbone treated groups. Non significant induction of total glutathione enzyme in the animals treated with zerumbone or celecoxib was detected. Similarly, there was no significant elevation in the level of malondialdehyde in the first three groups compared to fourth and fifth groups. Significant reduction of prostaglandin hormone following four weeks of oral administration of zerumbone and celecoxib compared to the negative control group was observed. Interestingly the levels of hormone in second group showed comparable level to those measured in the normal group.