This study aimed to investigate the potential role of IL-6 in acute T-cell-mediated renal rejection (ACR) during different periods post-transplantation. Fifty-three patients with ACR (32 of whom developed ACR within the first month; 12, between 2 and 6 months; and 9, between 7 and 12 months post-transplantation), 31 patients with delayed graft function (DGF), and 38 recipients with stable renal allograft function were recruited. Luminex analysis was used to monitor levels of IL-6, sIL-6R, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in 228 serum samples from 122 patients, including ACR patients before and during rejection, and after rejection reversal, DGF patients, and stable controls. The associations between IL-6 levels and sIL-6R, IL-1α, IL-1β, and IL-1Ra levels were analyzed using Spearman correlation analysis. In patients who developed ACR within the first month post-transplantation, serum IL-6 concentrations increased significantly compared to the stable control group, but decreased in patients who developed ACR between 2 and 12 months post-transplantation. Concomitantly, levels of sIL-6R gradually increased when ACR occurred between 2 and 12 months post-transplantation. IL-6 levels correlated with IL-1β levels in early stage ACR and with levels of IL-1Ra in late stage ACR. Our results suggest that IL-6 acts as a pro-inflammatory cytokine during early-stage ACR, and plays an anti-inflammatory role during later stages post-transplantation.