The role of peroxiredoxin (Prx) I as an erythrocyte antioxidantdefense in red blood cells (RBCs) is controversial. Here weinvestigated 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 bodyformation as compared with Prx II–⁄– mice. The clearance rate ofHeinz body-containing RBCs in Prx I–⁄– mice decreasedsignificantly through the treatment of aniline hydrochloride (AH)compared with wild-type mice. Prx I deficiency decreased thephagocytic capacity of macrophage in clearing Heinz bodycontainingRBCs. Our data demonstrate that Prx I deficiency didnot cause hemolytic anemia, but showed that further increasedhemolytic anemia symptoms in Prx II–⁄– mice by attenuatingphagocytic capacity of macrophage in oxidative stress damagedRBCs, suggesting a novel role of Prx I in phagocytosis ofmacrophage.