BACKGROUND Little is known regarding the impact of host response in acute pancreatitis. Here, we induce murine necrotizing pancreatitis in 9 different mouse strains. MATERIALS AND METHODS We examined 9 different mouse strains: Balb/CB4J, C3H/HEJ, NOD/SHILT, A/J, AKR/J, C57BI/6J, DBA/2J, FVB/NJ, 129S1/SvlmJ. 10 animals per strain were randomly allotted to two groups. Sterile necrotizing pancreatitis was induced by injection of taurocholate into the common bile duct. Control animals were injected with saline. Every 6 h, clinical parameters were examined and scored. After 24 h, animals were sacrificed to examine and compare serum enzymes, histology, bronchoalveolar lavage fluid, and serum IL-6. RESULTS Histologically, taurocholate treated animals scored significantly higher than control animals. Concordantly, serum lipase and amylase were significantly elevated in pancreatitis animals in all strains. NOD/SHILT and AKR/J mice had the highest enzyme activity. 24 h after induction, there were no signs of increased pulmonary vascular leak in taurocholate animals. Remarkably, interleukin 6 was not increased at all in C57BL/6J, C3H/HeJ, and 129S1/SvlmJ mice compared to all other strains. CONCLUSION The genetic strain has an impact on pancreatitis severity and systemic inflammatory response in a murine taurocholate induction model. Analogous differences in humans may partially account for the disparity in post-ERCP pancreatitis.