Antibody-mediated rejection (AMR) has been recognized as a significant cause of acute and chronic lung allograft dysfunction after lung transplantation. Some treatments, eculizumab, an anti-complement (C)5 component monoclonal antibody (Mab), seem to have a promising effect in the management of some patients with AMR. We present two patients with acute AMR after lung transplantation who received the anti-C5 Mab therapy. In both cases, we identified the presence of C4d deposition in the peritubular capillaries on trans-alveolar biopsies, which suggested activation of complement in AMR. Prior to eculizumab therapy, both patients had also received immunoadsorption, courses of intravenous immunoglobulins (IVIG) and rituximab. For the first patient, we have shown that eculizumab can serve as an effective bridge to re-transplantation. For the second patient, we observed the absence of clinical and biological efficacy, and without a clear therapeutic efficacy the therapy with eculizumab had been discontinued after two months.