In order to study the effects and mechanism of florfenicol (FFC) on the kidney function of broilers, 180 1-day-old broilers were randomly divided into 6 groups, 30 in each group. Except for the control group, different doses of FFC were added to drinking water in the other 5 groups (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L and 1.8 g/L). After continuous administration for 5 days, renal histopathological changes, serum renal function indicators, renal peroxidation products and antioxidant factors, and apoptotic factors were detected in broilers aged 21 and 42 days. The results showed that compared with the control group, the kidney tissue structure was disordered, the glomerulus was atrophic, the cystic cavity was enlarged, and the epithelial cells of renal tubules were seriously vacuolated in broilers of treatment groups. And with the growth of broilers, the kidney injury of broilers in the low-dose FFC group was relieved. FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum and malondialdehyde (MDA) in kidney of broilers, but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in kidney. FFC significantly inhibited the mRNA relative transcriptional levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3 and Caspase-6 in kidney tissue of broilers. It is concluded that FFC has certain nephrotoxicity to broilers, and its effect on kidney is dose-dependent and reversible. FFC causes intense lipid peroxidation in broiler kidney by inhibiting the expression of related factors in the downstream signal pathway of Nrf2. FFC can also up-regulate the expression of pro-apoptotic factors and accelerate the abnormal apoptosis of renal cells, thus seriously affecting the renal function of broilers.Copyright © 2020 Elsevier Inc. All rights reserved.