Abstract: Objective To investigate the permeability of cefpiramide (CPM) through blood-pancreatic barrier in the mice with sever acute pancreatitis(SAP). Methods CPM (42.5 mg·kg^-1 body weight) was intravenous injected to mice after abdominally injecting L-arginine to induce sever acute pancreatitis while normal saline injection as control. At the given time points, the serum and pancreatic samples were collected. The concentrations of CPM in the samples were measured by HPLC. Results The disposition of CPM in two groups fitted one compartment model. The average penetration ratios (PR) of the drug through the blood-pancreas barrier in normal control group was (49.2±38.4)%. The parameters in plasma were as follows: t1/2 1.42 h, C0 59.93 mg·L^-1, AUC0-∞ 122.73 mg·h·L^-1, and those in tissue were as follows: t1/2 1.14 h, C0 22.58 mg·kg^-1, AUC0-∞ 69.88 mg·h·kg^-1. In SAP group, there was no significant difference in average PR、t1/2、C0 and AUC0-∞ of CPM in the tissue compared with the normal control group (P >0.05). Conclusion CPM was shown to have a fairly high distribution in the pancreas in the SAP mice. It is therefore proposed that CPM may be used clinically for the prevention and treatment of pancreatic infection.