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Saikosaponin a (SSa), a triterpene saponin extracted from Bupleurumfalcatum L. , has been reported to have anti-inflammatory activity. In the present study, we investigated the effects of SSa on lead-induced kidney injury in common carp. Kidney histological changes were detected by H&E staining. The levels of TNF-α, IL-1β, MPO, MDA, GSH, and SOD activity were also measured. Furthermore, the NF-κB and Nrf2 signaling pathways were tested by western blot analysis. The results showed that lead-induced kidney histological change was attenuated by SSa. Lead-induced TNF-α, IL-1β, MPO, and MDA production were also suppressed by SSa. Meanwhile, lead could decrease GSH level and SOD activity and the decreases were inhibited by SSa. Furthermore, we found SSa significantly inhibited lead-induced NF-κB translocation. In addition, the expression of Nrf2 and HO-1 were increased by the treatment of SSa and Keap1 expression was decreased by SSa. In conclusion, this study indicated that SSa inhibited lead-induced kidney injury in carp through suppressing inflammatory and oxidative responses, and the mechanism may be involved in the inhibition of NF-κB and activation of Nrf2 signaling pathway. Unlabelled Image • Saikosaponin a (SSa) significantly inhibited lead-induced TNF-α, IL-1β, MPO, and MDA production. • The activity of SOD and the content of GSH were increased by SSa. • SSa dose-dependently suppressed lead-induced NF-κB activation. • SSa increased Nrf2 and HO-1 expression in a dose-dependent manner. [ABSTRACT FROM AUTHOR]