The timely and effective treatment for severe acute pancreatitis (SAP) is favorable to prognosis. Decompression of the bile duct might be a feasible way to decrease the progression of SAP. The present study investigated the effects of sustained bile external drainage on organs injury caused by SAP in Sprague-Dawley (SD) rats and the mechanisms involved. A total of 72 female SD rats weighting 190-230 g were randomly divided into four groups (n=18): Sham operation group (SOG), SOG + bile drainage group (BDG), SAP group, and SAP + BDG. Sodium taurocholate solution (4%; 1 mg/kg body weight) was used to set up SAP model via injection of retrograde puncture of biliopancreatic duct through the duodenum. A cannula was inserted into the bile duct and fixed externally to establish BDG model. At each time points (t=3, 6, 12; n=6), tissues from the liver, lung, and pancreas, and blood samples were collected. Serum amylase (AMY) was analyzed in all the samples. The levels of tumor necrosis factor-α (TNF-α), heme oxygenase-1 (HO-1), interleukin-10 (IL-10) and high mobility group box 1 (HMGB1) were detected by ELISA. Hematoxylin-eosin staining was performed to observe the histopathological changes, and nuclear transcription factor (NF)-κB-p65 levels in the pancreas were analyzed by western blotting. The data indicated that BDG alleviated the SAP progression and multiple organs injuries. Meanwhile, the histopathological changes of the pancreas, liver, and lungs were improved by BDG. BDG decreased the pathological scores of pancreas significantly (P<0.05). The levels of AMY, TNF-α, HMGB1, and NF-κB-p65 were significantly downregulated by BDG (P<0.05), while the level of HO-1 was upregulated and IL-10 was unchanged. In summary, BDG may attenuate the multiple organs injuries caused by SAP via downregulation of TNF-α, HMGB1, NF-κB-p65 and upregulation of HO-1.