Objective To investigate the change of intestinal barrier function and the protection of pentoxifylline (PTX) to intestinal barrier. Methods Fifty-four SD male rats were randomly divided into 3groups, including sham operation group, ANP group, PTX group. ANP rat model were induced by retrograde injection of 5% sodium taurocholate into pancreatic and bile duct. Rats in sham operation group underwent operation without injection of taurocholate. After ANP induction, the rats in PTX group received PTX at a dose of 25 mg/kg weight via penis vein. The rats were sacrificed 3, 6, 24 h after operation, the serum levels of amylase, D-lactic acid, TNF-α were determined. The pancreas tissue and terminal ileum were harvested for pathological examination; ZO-1 levels of ileum epithelial tight junction were analyzed by immunohistochemistry. Results Six hours after induction, the serum levels of amylase, TNF-α, D-lactic acid in ANP group were(9141±672)U/L, (347.96±79.47) pg/ml and (10.21±1.08 ) rmg/L, which were significantly higher than those in sham operation group [(1723 ± 57 )U/L, (134.09 ± 31.36 )pg/ml and (4.33 ±0.49)mg/L, P ＜0.01]. The serum levels of amylase, TNF-α, D-lactic acid in PTX group were (7965 ± 318 ) U/L, (238.48 ± 44.35 ) pg/ml and ( 8.75 ± 1.28 ) mg/L, which were significantly lower than those in ANP group, but they were significantly higher than those in sham group ( P＜0.05 or ＜0.01). The positive rate of ZO-1 was (3.29±0.36)% in sham operation group, and it was (1.91 ± 0. 32)% in ANP group,which was significantly lower than that in sham operation group (P ＜ 0.05 ); and the value was (2.53±0.43)%in PTX group, which was lower than that in sham group, but it was higher than that in ANP group(P＜0.05).Conclusions PTX may attenuate intestinal barrier function injury by decreasing the breakdown of intestinal ZO-1.