Objective To investigate the protective effect of combination of Ligustrum lucidum and Epimedium brevicornum (herb pair) on rat nephrotoxicity induced by cisplatin. Methods Wistar male rats were randomly divided into control group，model group and herb pair group，with 10 rats in each group. Except the control group，the other two groups were intraperitoneally injected with 3 mg/kg cisplatin on day 4； rats in herb pair group were given 350mg/kg extract intragastric administration 3 days before cisplatin for 7 consecutive days. After sampling，the change rate of body weight and organ index of rats were calculated，renal function indexes and histopathological changes were investigated. Immunohistochemistry was used to observe the expression and distribution of positive signals of kidney injury molecule – 1 (KIM-1) and anti-NADPH oxidase 4 (NOX4) in the kidney of rats. Western Blot was used to detect the effects of KIM-1 and NOX4 protein expression. The changes of malondialdehyde (MDA)，superoxide dismutase (SOD)，catalase (CAT)，reduced glutathione (GSH) and NADP+/NADPH in rat kidney tissue were detected by kit microassay. The effects of herb pair on Interleukin-1b (IL-1b)、Interleukin-6 （IL-6）and tumor necrosis factor-a (TNF-a) in kidney tissues of rats were determined by ELISA. Results Compared with the control group，cisplatin significantly reduced the body weight and levels of SOD，CAT，GSH，and TNF - α in the renal tissue of rats (P < 0.05)，The levels of renal organ index，serum blood urea nitrogen (BUN)，creatinine (CREA)，and renal tissue MDA，NADP+/NADPH，IL-1 β，and IL-6 were significantly increased (P < 0.05)，HE staining microscope showed that the renal tubular epithelial necrosis were necrotic and exfoliated，and the lumen was deformed and vacuolized，KIM-1 and NOX4 positive signals and protein expression were significantly increased (P < 0.05)； Compared with the model group，the intervention of Ligustrum lucidum and Epimedium herb significantly increased the levels of SOD，CAT，GSH，and TNF-a in renal tissue (P < 0.05). The renal organ index，serum BUN，UA，and renal tissue MDA，NADP+/NADPH，IL-6 levels significantly decreased (P < 0.05). HE staining of renal tissue showed a reduction in damage and a significant decrease in KIM-1 and NOX4 positive signals and protein expression (P < 0.05). Conclusion The combination of Ligustrum lucidum and Epimedium brevicornum exerted a protective effect against cisplatin-induced renal toxicity through inhibiting the expression of KIM-1 in kidney tissue

activating the activity of antioxidant enzymes

and suppressing the release of inflammatory factors.