Objective To investigate the effects of mirabilite external application combined with ulinastatin on intestinal barrier function, pancreatic cell activity and PI3K/Akt/mTOR signal in rats with pancreatitis. Methods Fifty SPF SD male rats were randomly divided into normal (N) group, model (M) group, glauberatin external application (G) group, ulinastatin (U) group, and glauberatin external application + ulinastatin (O) group, with 10 rats in each group. The model of pancreatitis was established in groups M, G, U and O by retrograde injection of 5% sodium taurine cholate through pancreatic duct. Group N does not build this model. After the modeling was successful, group G was given external application of glauberatin, group U was given intraperitoneal injection of ulinastatin 50,000 U/kg, group O was given external application of glauberatin and intraperitoneal injection of ulinastatin 50,000 U/kg, group N and group M were given intraperitoneal injection of normal saline of the same volume at the same time. The histopathologic morphology of pancreas was detected by HE method. The intestinal barrier function was detected by electron microscopy. Pancreatic cell apoptosis was detected by TUNEL assay. The expression of PI3K/Akt/mTOR signal-related proteins was detected by Western blotting. Results Compared with group N, the pathological changes of pancreatic tissue and intestinal barrier function were observed in group M. Compared with group M, the pathological morphology and intestinal barrier function of group G, group U and group O were significantly improved, and the improvement of group O was the most obvious. Compared with group N, the intestinal mucosal injury degree and the protein expressions of PI3K, p-Akt and p-mTOR in pancreatic tissue of rats in group M were significantly increased (P<0.05), and the apoptosis level of pancreatic cells was significantly decreased (P<0.05). Compared with group M, the intestinal mucosal injury degree and the protein expressions of PI3K, p-Akt and p-mTOR in pancreatic tissue of groups G, U and O were significantly decreased (P<0.05), and the apoptosis level of pancreatic cells was significantly increased (P<0.05), and there was no significant difference between group U and group G (P> 0.05). The changes in group O were significantly higher than those in group U (P<0.05).Conclusion External application of Mirabilite combined with ulinastatin can significantly improve intestinal barrier function and pancreatic cell activity in rats with pancreatitis, and significantly inhibit PI3K/Akt/mTOR signal