Sepsis, the most common cause of acute kidney injury, remains a major socioeconomic burden. A dysregulated immune response leads to progressive organ dysfunction. Although numerous inflammatory pathways were described, most are still vague and need to be studied in terms of the mechanisms to improve the therapeutic intervention. We tackled the relationship between intracellular iron overload and macrophage polarization within 6, 24, and 72 h of sepsis induction. In our study, sepsis-induced kidney injury was caused by using the cecal ligation and puncture (CLP) model. Our results indicated severe renal tissue damage with a progressive increase in serum BUN and creatinine with architectural tissue damage and positive PAS staining. There was increased expression of CD8