Abstract: Background and Objective: The kidney is an important organ highly susceptible to the toxic effects of different toxic substances. Esomeprazole is one of the proton pump inhibitors used in the treatment of gastrointestinal disorders but with many side effects. Carob is used in many Arab countries as a popular drink. Carob pod extract has an antioxidant and anti-inflammatory effect. This work aimed to investigate the possible protective effect of carob pod extract (Ceratonia siliqua) on Esomeprazole-induced changes in the renal cortex of adult male albino rats using histological and immunohistochemical studies. Materials and Methods: A total of 40 rats (100-150 g) were divided into four groups (10 rats each), control, carob group: Rats received 200 mg/kg/day carob pods extract, esomeprazole group: Rats received esomeprazole 20 mg/kg/day orally and carob and esomeprazole group: Rats received 200 mg/kg/day carob pods extract 1 hr before 20 mg/kg/day esomeprazole orally by intragastric tube. The collected data from the different experimental groups were analyzed by student’s t-test after evaluation of the F-test. Results: Esomeprazole group showed shrunken glomeruli, dilated Bowman’s space, dark tubular cell nuclei, cytoplasmic vacuolations and intraluminal cellular debris in toluidine blue stained sections, a significant decrease in the mean optical density for PAS, significant decreased iNOS immunoreaction and significant EM changes. Esomeprazole and carob groups showed improvement in the previous changes. Conclusion: Esomeprazole-induced structural changes in the renal cortex of rats and carob pod extract could improve such changes.