Aim The current study aimed to explore the pretreatment of bone marrow mesenchymal stem cells (BMSCs) with hyaluronic acid (HA) on renal fibrosis in Adriamycin- induced CKD in rats. Material and methods Sixty male SD rats were alienated into 4 equal groups; The control group: rats received two saline injections at 1 and 14 days, adriamycin (ADR) group: rats were injected i.v. twice via tail vein at day one and after 2 weeks, BMSCs group; rats were injected i.v. twice after 5 days of each ADR injection, and HA+BMSCs; rats were i.v. injected twice with BMSCs pretreated with 1 mg/ml HA after 5 days of each ADR injection. Protective role of BMSCs on renal function and morphology was detected using biochemical analysis, molecular studies, histopathological, and immunohistohemical investigations. Results Pretreatment of BMSCs with HA showed significant decrease in KIM-1, and increase in serum albumin compared to CKD group (p <0.05). Moreover, it reduced the expression of the apoptotic marker Caspase-3, the inflammatory markers TNF and IL-6, and the fibrotic markers Wnt7a, β-catenin, and fibronectin1 than the CKD group (p < 0.05). Conclusion The current outcomes suggested that BMSCs preconditioned with HA could attenuate the renal fibrosis in adriamycin- induced CKD.