This study aims to investigate the mechanism by which biliary drainage reduces intestinal barrier damage in obstructive jaundice (OJ). A biliary drainage model was established in rats with OJ to detect changes in inflammatory factors and diamine oxidase (DAO), a marker of intestinal mucosal damage. The expression of autophagy-related genes in the intestinal mucosa after biliary drainage was detected using a reverse transcription-polymerase chain reaction. The rats were separated into two groups that received the autophagy activator rapamycin (RAPA) or the autophagy inhibitor 3-methyladenine (3-MA) to further investigate whether biliary drainage could alleviate the inflammatory response, oxidative stress, mitochondrial complex IV damage, and thus barrier damage in rats with OJ. The expression levels of inflammatory factors and the serum DAO content were increased in rats with OJ (P < 0.05). Biliary drainage further induced autophagy, reduced the expression levels of inflammatory factors, decreased the serum DAO content (P < 0.05), and improved intestinal mucosal damage. Administration of RAPA to OJ rats with biliary drainage increased autophagy (P < 0.05); decreased inflammatory factor secretion (P < 0.05), the serum DAO content (P < 0.05), oxidative stress (P < 0.05), and mitochondrial respiratory chain complex IV damage (P < 0.05); and ameliorated intestinal mucosal injury in OJ rats. When OJ rats were treated with 3-MA, intestinal mucosal injury, intestinal mitochondrial injury, and oxidative stress were all aggravated (P < 0.05). Biliary drainage can reduce the expression of inflammatory factors, oxidative stress, and mitochondrial injury by inducing intestinal mucosal autophagy in OJ rats, thus suggesting its role in the alleviation of intestinal mucosal injury.