The present study summarizes three key findings: hepatic I/R in DM rats leads to oxidative stress and inflammation due to decreased antioxidant enzymes and elevated pro‐inflammatory cytokines; pretreatment with high‐dose SIN mitigates hepatic I/R damage in diabetic rats by reducing oxidative stress, inflammation, and improving liver function and pathology; and high‐dose SIN activates Nrf‐2/HO‐1‐mediated endogenous antioxidant stress/anti‐inflammation mechanism in these rats. Here, HMOX1 is linked to diabetes mellitus.