Renal fibrosis is a major pathological feature of chronic kidney disease (CKD) and contributes to the progressive and irreversible loss of renal function. It is characterized by excessive extracellular matrix deposition, tubular injury, and epithelial–mesenchymal transition (EMT)-associated changes. Histone deacetylase 6 (HDAC6) has emerged as a potential therapeutic target because of its involvement in profibrotic signaling. This study investigated the antifibrotic effects of WT-161, a selective HDAC6 inhibitor, in an adenine-induced mouse model of CKD. Renal fibrosis was induced by oral administration of adenine at 50 mg/kg/day for the first 7 days, followed by 25 mg/kg/day for an additional 3 weeks. To assess its therapeutic effects during established disease progression, WT-161 was administered intraperitoneally during 2 weeks. At the end of experiment, the mice were euthanized, and kidney tissues were collected for analyses. The expression of fibrosis- and EMT-associated proteins, including α-smooth muscle actin (α-SMA) and vimentin, was evaluated by western blotting. WT-161 treatment attenuated adenine-induced renal structural abnormalities and suppressed the expression of α-SMA and vimentin, indicating inhibition of renal fibrogenesis and EMT-associated changes. These findings suggest that pharmacological inhibition of HDAC6 by WT-161 alleviates adenine-induced renal fibrosis and may represent a promising therapeutic strategy for CKD-associated renal fibrosis.