Background: Sinusoidal obstruction syndrome is caused by an injury to the liver induced either by accidental ingestion of pyrrolizidine alkaloid monocrotaline or by chemotherapeutic drug oxaliplatin used for the treatment of colorectal cancer. Sinusoidal obstruction syndrome is characterized by rounding and swelling of the sinusoidal endothelial cell, which leads to obstruction of blood vessels, leukocyte infiltration, and oxidative stress. Melatonin, a powerful antioxidant, prevents acute liver injury. We investigated the effect of melatonin on monocrotaline-induced sinusoidal obstruction syndrome in mice. Methods: Male C57BL/6JNarl mice were injected with a single dose (500 mg/kg) of monocrotaline to induce sinusoidal obstruction syndrome. Melatonin (1-30 mg/kg) was injected 1 h before monocrotaline treatment. After 24 h of monocrotaline treatment, mice were sacrificed. Hepatic collagen, oxidative stress, antioxidant activity, and the expression of apoptosis protein were measured.