Renal fibrosis is a major factor in the progression of chronic kidney disease and the final common pathway of kidney injury. Therefore, the effective therapies against renal fibrosis are urgently needed. The objective of this study was to investigate the effect of Am80, a synthetic retinoic acid receptor (RAR) agonist, in the treatment of renal interstitial fibrosis using unilateral ureteral obstruction (UUO) mice. The findings indicate that Am80 treatment suppressed renal fibrosis and inflammation to the same degree as the naturally-occuring retinoic acid, all-trans retinoic acid (atRA). But the adverse effect of body weight loss in Am80-treated mice was lower compared to the atRA treatment. The hepatic mRNA levels of alpha-1-acid glycoprotein (AGP), a downstream molecule of RAR agonist, was increased following administration of Am80 to healthy mice. In addition, increased AGP mRNA expression was also observed in HepG2 cells and THP-1-derived macrophages that had been treated with Am80. AGP-knockout mice exacerbated renal fibrosis, inflammation and macrophage infiltration in UUO mice, indicating endogenous AGP played an anti-fibrotic and anti-inflammatory role during the development of renal fibrosis. We also found that no anti-fibrotic effect of Am80 was observed in UUO-treated AGP-knockout mice whereas atRA treatment tended to show a partial anti-fibrotic effect. These collective findings suggest that Am80 protects against renal fibrosis via being involved in AGP function. Approximately 10% of the world's population are affected by chronic kidney disease (CKD). CKD is associated with a risk of end-stage renal disease (ESRD), which is fatal without kidney replacement therapy such as dialysis or kidney transplantation 1,2. Renal fibrosis is the main factor in CKD progression and the final common pathway of kidney injury 3,4. Although initial fibrosis is thought to play a beneficial role in maintaining the kidney structure upon injury and repair 5 , the development of fibrosis causes a progressive decline in renal function 6. Therefore, effective therapies against renal fibrosis are urgently needed. It is known that retinoids, derivatives of vitamin A (retinol), regulate embryonic development and cellular differentiation 7. All-trans retinoic acid (atRA) is a natural retinoic acid that is clinically used for treating patients with acute promyelocytic leukemia. Retinoids are also of interest for their renoprotective and anti-inflammatory effects. In fact, atRA treatment was reported to suppress renal fibrosis in a unilateral ureteral obstruction