By using mice with Tfrc heterozygote knockout, astrocyte‐specific conditional Tfrc knockdown or conditional astrocytic Cpt1a partial knockout (to induce astrocytic fatty acid disorder), we uncover that after ischemic stroke, an increase in TfR1 palmitoylation and clathrin‐mediated TfR1 endocytosis results in elevated iron uptake and intracellular iron overload of astrocytes, and ischemic stroke‐induced increase in fatty acids, particularly, an elevated palmitic acid is associated with TfR1 palmitoylation enhancement. This evidence concerns the gene CPT1A and ischemic stroke.