This study aimed to evaluate the impact of Hyaluronic acid (HA) in enhancing the migration and the therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in chronic renal disease. Material and Methods: Sixty Sprague Dawley male rats were alienated into 4 equal groups; control group: rats received two saline injections at 1 and 14 days, Adriamycin (ADR) group: rats were injected iv twice via tail vein at day one and after 2 weeks, BMSCs group; rats were injected iv twice after 5 days of each ADR injection, and HA+ BMSCs group; rats were iv injected twice with BMSCs pretreated with 1mg/ml HA after 5 days of each ADR injection. Viability and proliferation of BMSCs was assessed, protective role of BMSCs on renal function and morphology was detected using biochemical analysis, Masson'strichrome staining and the apoptotic marker caspase-3. Results: HA was found to increase the BMSCs viability and proliferation than the untreated cells (p< 0.05). Meanwhile, serum creatinine, blood urea nitrogen and urinary protein excretion levels were significantly low in BMSCs preconditioned with HA compared to ADR (p< 0.05).Moreover, BMSCs treated with HA enhanced the renal regeneration, the antioxidants, and reduce the apoptosis compared to ADR group (p< 0.05). Conclusion: The results manifested that HA has the potentiality to enhance BMSCs viability and provides renal protection via improving the renal morphology and reduce the apoptosis and restore the balance between enzymes activity and free radicals.