BACKGROUND Hydatid disease is a worldwide health problem. Treatment is surgical or percutaneous, using scolicidal agents. Caustic sclerosing cholangitis might develop after the contact of scolicidal agents with the biliary ducts. Melatonin, an antioxidant, anti-inflammatory, and anticarcinogenic agent, might be used in the treatment of caustic sclerosing cholangitis due to its possible preventive effects on fibrosis and cell damage. OBJECTIVE The aim of the study was to investigate the effects of melatonin on an experimentally developed caustic sclerosing cholangitis with scolicidal solution (formalin) in a rat model. METHODS Forty female Sprague-Dawley rats aged 11 to 13 weeks and weighing 250 ± 30 g were randomly assigned to 1 of 4 groups of 10: formalin 5% at 0.5 mL/d + melatonin placebo; formalin placebo + intraperitoneal melatonin 10 mg/kg/d; formalin 5% at 0.5 mL/d + melatonin 10 mg/kg/d; and formalin placebo and melatonin placebo (control). Hepatobiliary function was assessed using dynamic scintigraphy with technetium-99m-mebrofenin on study day 60. The histology of the liver and biliary duct specimens was examined on study day 60. In each group, histopathologic alterations were scored as absent, slight, mild, or severe. RESULTS Mean severity scores for parenchymal necrosis in the liver (P < 0.01), portal fibrosis (P < 0.01), biliary duct proliferation (P < 0.001), cholangitis/ pericholangitis (P < 0.01), hyperemia in the biliary ducts (P < 0.01), and fibrosis (P < 0.01) were significantly lower in rats treated with formalin + melatonin compared with those treated with formalin alone. No significant differences were observed between the 3 treatment groups with respect to t½, a parameter used to assess the secretion function of the hepatocytes. However, the t½ was significantly longer in the treatment groups compared with controls (P < 0.001). CONCLUSIONS In this experimental study in a rat model of caustic sclerosing cholangitis, the histopathologic and scintigraphic findings suggested that melatonin is effective in attenuating the damage caused by scolicidal agents on the liver and biliary ducts.