Objective(s): This study aimed to investigate the possible effects of fetuin-A on an adenine-induced chronic kidney disease (CKD) model in male rats. Materials and Methods: Rats were divided into three groups: group A included rats fed a normal diet; group B included rats fed a normal diet with 220 mg/kg adenine daily for 21 days; group C included rats fed a normal diet with 220 mg/kg adenine daily for 21 days and intraperitoneally administered with 5 mg\kg fetuin-A every other day for 2 weeks. Serum samples were assayed for serum creatinine, urea, sodium, potassium, calcium, phosphorus, tumor necrosis factor (TNF), interleukin-6 (IL-6), and estimated glomerular filtration rate (eGFR), and immunohistochemical staining was performed. Results: Group B showed a significant increase in serum creatinine, urea, phosphorus, potassium, TNF, and IL-6 and a significant decrease in serum sodium, calcium, and eGFR compared with group A. Regarding immunohistochemistry, group B showed increased apoptosis. In group C, fetuin-A reduced the urea, creatinine, and phosphorus levels, and in group C, fetuin-A decreased inflammation and apoptosis by reduction of caspase-3 staining. Conclusion: Fetuin-A improved kidney function in CKD due to its anti-inflammatory and anti-fibrotic role.