Background: Sclerosing cholangitis is a rare but dreadful complication of liver hydatid surgery. Almost all scolicidal agents were shown to be potentially associated with this complication clinically or experimentally. This experimental study was designed to examine the effects of 0.04% chlorhexidine gluconate and 95% ethanol on the hepatobiliary system and pancreas and also to compare their effects with 10% povidone iodine and hypertonic 20% saline. Materials and Methods: 50 Wistar rats were divided into equal five groups identified as: 0.9% NaCl ( control group), 0.04% chlorhexidine gluconate, hypertonic 20% saline, 10% povidone iodine, and 95% ethanol. Scolicidal agents were injected into the biliary tract through a duodenal puncture. The animals were kept for 3 months. The animals were sacrificed, and histopathological examinations of the liver, biliary tract, and pancreas were performed. Results: The most severe histopathological changes of the liver, biliary tract, and pancreas were found in the ethanol group, and the least changes were detected in the chlorhexidine gluconate group. Conclusion: This experimental study confirms the deleterious effect of 95% ethanol on hepatopancreatic biliary system when used for the percutaneous drainage of hydatid diseases. For treatment of hydatid cysts in the hepatobiliary system, 0.04% chlorhexidine gluconate should be used as scolicidal agent.