Apelin is a vasoactive peptide isolated as a selective endogenous ligand of APJ receptor. The effects of the apelin/APJ system on renal fibrosis still remain unclear. We administered apelin in a unilateral ureteral obstruction (UUO) model of mouse and examined its effects on pathological changes related to renal fibrosis. The protein expression of APJ receptor in the UUO kidney was upregulated within 7 days following ureteral ligation. Treatment with apelin resulted in an attenuated renal interstitial fibrosis, a decreased myofibroblast accumulation, and a decreased tubular apoptosis, along with increased phospho-endothelial nitric oxide synthase (eNOS) and phospho-Akt protein expressions in the UUO kidney on day 7 after UUO without affecting blood pressure. When mice were treated with a NOS inhibitor, L-NAME, concomitantly with apelin, the degrees of renal fibrosis, myofibroblast accumulation, tubular apoptosis, and interstitial macrophage infiltration were all rather increased compared with the control mice with no treatment. These findings suggest that exogenous infusion of apelin ameliorates renal fibrosis in an early stage of obstructive nephropathy, at least in part, through the nitric oxide (NO)-dependent mechanism.