ABSTRACT Introduction: Mirabegron is a novel β3-adrenergic receptor agonist that recently approved for the management of overactive urinary bladder disease. Reactive oxygen species (ROS) have a major role in the pathogenesis of gentamicin nephrotoxicity. The aim of the present study was to investigate the renoprotective effect of mirabegron alone and in combination with N-acetylcysteine (NAC) in cases of nephrotoxicity induced by gentamicin in rats. Materials and Methods: 40 Wistar rats were divided into 5 groups. Group 1; treated with NaCl 0.2 ml i.p. Group 2; received 100 mg/kg of gentamicin i.p. for 8 days for induction of nephrotoxicity. Group 3; treated with gentamicin + NAC (500 mg/kg i.p.for 8 days). Group 4; treated with gentamicin + mirabegron (10 mg/kg orally for 8 days). Group 5; treated with gentamicin + NAC + mirabegron. After 8 days, blood samples were used for assessment of renal function. Serum nitric oxide, renal malondialdehyde (MDA) and glutathione (GSH) levels were measured. Results: Gentamicin caused a significant elevation of serum creatinine, urea, uric acid and nitric oxide with significant elevation of kidney MDA with reduction of GSH. Treatment with both of NAC and mirabegron each alone or in combination with each other caused restoration of renal function parameters and caused significant decrease in serum nitric oxide and MAD and increase in GSH. These changes were more marked with combination of NAC and mirabegron. Conclusion: Mirabegron has a modest antioxidant activity which may be responsible for its protective effect against nephrotoxicity induced by gentamicin.