The role of peroxiredoxin (Prx) I as an erythrocyte antioxidant defense in red blood cells (RBCs) is controversial. Here we investigated the function of Prx I by using Prx I-/- and Prx I/II-/- mice. Prx I-/- mice exhibited a normal blood profile. However, Prx I/II-/- mice showed more significantly increased Heinz body formation as compared with Prx II-/- mice. The clearance rate of Heinz body-containing RBCs in Prx I-/- mice decreased significantly through the treatment of aniline hydrochloride (AH) compared with wild-type mice. Prx I deficiency decreased the phagocytic capacity of macrophage in clearing Heinz bodycontaining RBCs. Our data demonstrate that Prx I deficiency did not cause hemolytic anemia, but showed that furtherincreased hemolytic anemia symptoms in Prx II-/- mice by attenuating phagocytic capacity of macrophage in oxidative stress damaged RBCs, suggesting a novel role of Prx I in phagocytosis of macrophage.