(Pro)renin receptor ((P)RR) is a specific receptor for renin and prorenin (Ngyen et al. 2002). When prorenin binds to (P)RR, prorenin becomes enzymatically active in converting angiotensinogen to angiotensin I. In addition, (P)RR has various biological functions independent of the renin-angiotensin system. The binding of (pro)renin to (P)RR stimulates the intracellular signals for proliferation and/or hypertrophy of cells. (P)RR is associated with vacuolar-type H+-ATPase, a large multi-subunit, membrane-associated protein complex which keeps the acidic environment of intracellular compartments and of the extracellular space. Soluble (P)RR (s(P)RR) is generated by the cleavage of full length (P)RR consisting of 350 amino acids with a single transmembrane domain. (P)RR is expressed in various types of cells including erythroid cells. (P)RR is related to the pathophysiology of vascular complication of diabetes mellitus and hypertension. Moreover, plasma levels of s(P)RR were elevated in patients with obstructive sleep apnea syndrome (Nishijima et al., 2014). However, the mechanism which controls plasma s(P)RR levels has not been clarified. The aim of the present study is therefore to clarify effects of oxidative stress on generation of s(P)RR in erythroid cells. Human cultured erythroid cell line, YN-1 (Kaneko et al., 2012) was cultured in Iscove’s modified Dulbecco’s medium containing fetal bovine serum. The cells were treated with H2O2 (10, 100, 1000 µM) for 24h. (P)RR expression was analyzed by western blot analysis using the rabbit polyclonal (P)RR antibody specific for its extracellular domain (Hirose et al. 2009). The effect of erythropoietin (EPO, 10 ng/ml) on s(P)RR levels was also studied. Western blot analysis (n=4) showed that expression levels of s(P)RR (28 kDa) were increased about 21-fold by the treatment of 1000 µM H2O2 compared with control. EPO (10 ng/ml) alone did not affect expression levels of s(P)RR. Co-treatment of EPO (10 ng/ml) and H2O2 (1000 µM), however, suppressed the H2O2-induced increase in s(P)RR expression level to about 33%. Expression levels of furin protein were not changed by any treatments, suggesting that H2O2-induced increase in s(P)RR expression level was not mediated by the expression level of furin. These findings raised the possibility that oxidative stress increased expression levels of s(P)RR and that EPO played an protective role against oxidative stress.