This study investigates the mechanism of concanavalin A (Con A)-induced liver injury in mice. Intravenous administration of Con A (>1.5 mg/kg) led to severe liver injury characterized by elevated transaminase levels and histopathological changes, primarily affecting the liver. Electron microscopy revealed leukocyte adherence to endothelial cells and bile formation in hepatocytes. The hepatotoxicity was not correlated with Con A's agglutination activity or sugar specificity. Pharmacological interventions, such as dexamethasone, FK 506, and cyclosporine A, protected the animals, while indomethacin failed to provide protection. Con A hepatitis was associated with IL-2 release into the serum. Lymphocyte-deficient mice (SCID and athymic nude) were resistant to Con A-induced liver injury, and pretreatment with anti-T lymphocyte antibodies also protected against the injury. The involvement of macrophages was confirmed by silica particle treatment, which prevented Con A-induced hepatitis. These findings suggest that Con A-induced liver injury depends on the activation of T lymphocytes by macrophages, providing a model for studying immunologically mediated hepatic disorders.This study investigates the mechanism of concanavalin A (Con A)-induced liver injury in mice. Intravenous administration of Con A (>1.5 mg/kg) led to severe liver injury characterized by elevated transaminase levels and histopathological changes, primarily affecting the liver. Electron microscopy revealed leukocyte adherence to endothelial cells and bile formation in hepatocytes. The hepatotoxicity was not correlated with Con A's agglutination activity or sugar specificity. Pharmacological interventions, such as dexamethasone, FK 506, and cyclosporine A, protected the animals, while indomethacin failed to provide protection. Con A hepatitis was associated with IL-2 release into the serum. Lymphocyte-deficient mice (SCID and athymic nude) were resistant to Con A-induced liver injury, and pretreatment with anti-T lymphocyte antibodies also protected against the injury. The involvement of macrophages was confirmed by silica particle treatment, which prevented Con A-induced hepatitis. These findings suggest that Con A-induced liver injury depends on the activation of T lymphocytes by macrophages, providing a model for studying immunologically mediated hepatic disorders.