Abstract Background and Aims Chronic active antibody-mediated rejection (cABMR) is a leading cause of allograft failure in kidney transplantation (KT) recipients. However, no effective treatment has been established to date. This study investigated the effectiveness and safety of tocilizumab (TCZ), an anti-IL-6 receptor antibody, in delaying cABMR progression in KT recipients. Method We included 18 KT recipients with cABMR who were treated with TCZ. TCZ was administered monthly at a dose of 8 mg/kg (up to maximum of 800 mg) for 6 months (Fig. 1). The primary outcome was allograft survival, and patients were divided into responders (no allograft failure within a year) and nonresponders (allograft failure within a year). Secondary outcomes included changes in the estimated glomerular filtration rate (eGFR), proteinuria, mean fluorescence intensity (MFI) of anti-HLA antibodies, and adverse events (AEs). Baseline characteristics and outcomes were compared between responders and nonresponders. Results Allograft failure occurred in 44.4% (8/18) patients (Fig. 2A). All nonresponders experienced early allograft failure (mean 5.2 months), while 23.1% (3/13) of responders experienced allograft failure at a mean of 16.1 months post-treatment (Fig. 2B). Initial eGFR was significantly lower in nonresponders compared responders (15.9 mL/min/1.73 m2 vs. 34.4 mL/min/1.73 m2, p = 0.011) and was the only significant predictor of allograft failure (hazard ratio: 0.854, 95% confidence interval: 0.791–0.959). In the receiver operating characteristic (ROC) curve analysis using eGFR at treatment initiation (Fig. 2C), the area under the curve (AUC) was 0.900 (95% confidence interval [CI], 0.740–1.000; p < 0.05). The optimal cutoff value for predicting allograft failure was determined to be an eGFR of 25.5 ml/min/m2, with a sensitivity of 87.5% and a specificity of 90.0%. MFI levels of anti-HLA antibodies decreased in both responders and nonresponders (Fig. 3A). However, TCZ slowed eGFR decline and reduced proteinuria only in responders, while demonstrating no effectiveness in nonresponders (Fig. 3B, 3C, and 3D). No immediate side effects were observed. AEs included infections (n = 5), hypogammaglobulinemia (n = 6), and leukopenia (n = 2), with TCZ discontinued in one case of severe leukopenia. Conclusion TCZ should be selectively used in patients with preserved allograft function, considering the limited evidence, potential risks, and substantial costs.