Collectively, our current study first elucidated that SKI and its main components including chrysophanol, emodin, and rhein protected against renal fibrosis by inhibiting oxidative stress and inflammation via simultaneous targeting pro-inflammatory IƙB/NF-ƙB and anti-inflammatory Keap1/Nrf2 signaling pathways, which revealed the underlying molecular mechanism of SKI and its main components against renal fibrosis. Here, KEAP1 is linked to renal fibrosis.