Sclerosing cholangitis is a rare but dreadful complication of liver hydatid surgery. Almost all scolocidal agents are associated clinically or experimentally with this complication. Cetrimide-chlorhexidine combination is the most potent scolocidal agent, and this study was designed to examine its effect on the hepato-pancreatico-biliary system. Forty Wistar-albino rats were divided into two groups. 0.5% cetrimide-0.05% chlorhexidine was injected into the biliary tract of study group animals and 0.9% saline (NaCl) into the control group through a 3-mm duodenotomy. The animals were sacrificed after 90 days and histopathological examination of the liver, biliary tract, and pancreas was performed 90 days after the biliary injection. The histopathological examination showed that the lesions ranged from focal necrosis to sclerosing cholangitis to liver cirrhosis. Focal necrosis and eosinophilic inflammation were observed in all rats in the study group. The changes in the liver, biliary tract, and pancreas of the study group animals were significantly more severe than those in the control group (p < 0.05). This experimental study confirms the deleterious effect of another scolocidal agents on the hepato-pancreatico-biliary system. Although it is a very effective scolocldal agent, it should not be used in the presence of a duct biliary-cyst communication.