•Histopathological changes and the increase in serum creatinine and BUN induced by cisplatin were ameliorated by berberine.•Berberine significantly reduced the increase in renal CYP2E1, 4-HNE, 3-NT and HO-1 expression.•The expression of NF-κB, TNF-α and COX-2 in the kidneys was markedly suppressed by berberine.•Treatment with berberine reduced the expression of p53, cleaved caspase-3 and LC3B in the kidneys.•Berberine inhibited renal oxidative stress, inflammation, apoptosis and autophagy induced by cisplatin. The aim of this study was to investigate the therapeutic activity of isoquinoline alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice. Berberine was administered at daily doses of 1, 2 and 3mg/kg by gavage for two successive days, 48h after intraperitoneal CP injection (13mg/kg). Mice were sacrificed 24h after the last dose of berberine. Histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were significantly ameliorated by berberine in a dose-dependent manner. Additionally, oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced. The expression of nuclear factor-kappaB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by berberine, indicating the inhibition of inflammatory response. Treatment of CP-intoxicated animals with berberine also significantly reduced the expression of p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the kidneys. The results of the current study showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.