Introduction Liver transplantation is currently an increasingly popular treatment method for patients with liver failure, both in adults and children. Antibody-mediated rejection (AMR), which is a very rare and poorly understood phenomenon, can lead to deterioration of graft function. The aim of the study was to analyze the clinical and histopathological manifestation of AMR in pediatric patients. Material and methods Sixty-two liver core biopsies from forty-two pediatric patients were included in this retrospective study. AMR was diagnosed in 7 children (in 10 biopsies), 35 demonstrated features of acute T-cell mediated rejection (TCMR) in 52 biopsies. C4d binding assay was performed in all biopsies using the immunohistochemical (IHC) method. The specimens were re-evaluated for signs of acute and chronic rejection, bilirubinostasis, and steatosis. Fibrosis was evaluated using a 6-grade Ishak scale. The Banff classification was used to assess TCMR activity. Evaluation of AMR was performed according to a newly developed original histopathological grading. Relationship between histopathological grading and morphological, as well as laboratory parameters was determined in each group depending on type of rejection. Statistical analysis was performed according to standard indications. Results The median age of patients (months) at the time of biopsy was 47.6 (15.03 – 98.83) and the median time from transplantation (months) was 0.9 (0.3 – 7.6). Results of the study brought evidence that histopathological lesions were the least specific manifestation suggesting AMR. Positive result of C4d staining with or without associated morphological abnormalities statistically increases the likelihood of AMR diagnosis. No statistically significant correlation was found between the type of rejection and laboratory tests. Conclusions: Diagnosis of AMR in transplanted liver is complicated and need to be complex. However, the proposed histopathological grading may be a helpful method for selecting patients who should be assessed for Donor-specific antibodies (DSAs) or in whom AMR should be suspected when DSA cannot be determined.