Background: Chronic kidney disease (CKD) is a major public health problem worldwide. The pathophysiological basis of the disease and its complication include inflammation and oxidative stress, which are similar in humans and animals. In this study, we seek to develop new therapeutic modalities for CKD. Aim of the work: This study aimed to investigate the ameliorative effects of propolis (Prop) in experimental adenine (AD) induced model of CKD. Materials and methods: Twenty-four Sprague-Dawley rats were allocated into four equal groups as following: control group, AD group received adenine 200 mg/kg/day orally for 28 days to induce CKD, (Recovery group) received AD as previous group then left untreated for another 14 days. (Prop treated group) received Propolis 100 mg/kg b.w/ day in addition to AD for 28 days. At the end of experiment, body weight and kidney weight were estimated for all groups. In addition, blood samples were obtained to estimate serum urea and creatinine. kidney function tests, oxidative stress markers and levels of miRNA-21-5p, miRNA-103a-3p, miRNA-192-5p were evaluated. Histopathological measurement of renal tissues and immunohistochemical staining for tumor necrosis factor‑α were performed. Results: Propolis significantly decreased body weight loss and urine volume and improved renal hemodynamic changes caused by AD. In addition, it significantly improved kidney function tests and biomarkers of oxidative stress. A significant decrease of P53 immunohistochemical demonstration was documented. It also apparently reduced histopathological changes induced by AD. Conclusion: Propolis may play a promising role in renal tissue structural and functional preservation in AD‑induced chronic kidney disease, making it a desirable supplement.