The benefit of biological therapies in rheumatoid arthritis (RA) treatment is well known, but their role in amyloid A (AA) amyloidosis secondary to RA is unclear. The aim of this study was to clarify the clinical benefit of etanercept in RA patients with AA amyloidosis. We treated 14 RA patients who had serum amyloid A protein (SAA) 1.3 allele, with biopsy-confirmed AA amyloidosis with etanercept and investigated the efficacy of etanercept treatment, focusing on renal function retrospectively. The AA amyloidosis improved and stabilized after 89.1 ± 27.2 weeks. Proteinuria decreased from 2.24 ± 0.81 to 0.57 ± 0.41 g/day (P < 0.01) and SAA fell from 250 ± 129 to 26 ± 15 μg/ml (P < 0.01), respectively. Diarrhea secondary to gastrointestinal AA amyloidosis was less. Overall, the serum creatinine levels did not benefit with treatment, but in those with a creatinine values <2.0 mg/dl the creatinine level continued to fall (P = 0.021). Serum albumin increased following 96 weeks of etanercept treatment (P = 0.003). Etanercept treatment led to clinical improvement in proteinuria and serum albumin levels accompanied by a fall in SAA levels.