ObjectiveTo explore the protective effect of rapamycin on pancreatic damage in severe acute pancreatitis (SAP) and further to explain its protective mechanism.MethodsNinety selected SPF males SD rats were randomly divided into 3 groups: sham-operated group (SO group), SAP group, and rapamycin group (RAPA group), with 30 rats in each group. Then each group of rats were randomly divided into 3 subgroups of 24 h, 36 h, and 48 h, 10 rats in each subgroup. Rats in each group underwent laparotomy, the model was prepared by retrograde injection of solutions into biliopancreatic duct, rats of the SO group were injected with 0.9% normal saline, rats of the SAP group and RAPA group were injected with 5% sodium taurocholate solution, but rats of the RAPA group were injected with rapamycin at 30 min before the injection of 5% sodium taurocholate. All the survival rats in corresponding subgroup were killed at 24 h,36 h, and 48 h after operation respectively, then serum and pancreas tissues of rats were collected, serum inflammatory factors content of IL-1β, IL-6, and TNF-α were detected by ELISA method, expression levels of p-mTOR and p-S6K1 in pancreas were detected by Western blot, pancreas tissues were stained by Hematoxylin-Eosin Staining and pathological changes of pancreas were scored under light microscope.Results① At the timepoint of 24 h, 36 h, and 48 h, the order of the expression levels of p-mTOR and p-S6K1 in pancreatic tissues of 3 groups were all as follows: SO group<RAPA group<SAP group, there were significant difference among any 2 groups (P<0.05). ② IL-1β: at the timepoint of 48 h, the order of the content of IL-1β in 3 groups were as follows: SO group<RAPA group<SAP group, there were significant differences among any 2 groups (P<0.05); IL-6: at the timepoint of 36 h and 48 h, the order of the content of IL-6 in3 groups were as follows: SO group<RAPA group<SAP group, there were significant differences among any 2 groups (P<0.05); TNF-α: at the timepoint of 48 h, the order of the content of TNF-α in 3 groups was as follows: SO/RAPA group<SAP group (P<0.05), but there was no significant difference between the SO group and RAPA group (P>0.05). ③ Pancreatic histological score: at the timepoint of 24 h, 36 h, and 48 h, the order of the pancreatic histological score in3 groups was all as follows: SO group<RAPA group <SAP group, there were significant differences among any 2 groups (P<0.05). ④ The expression levels of p-mTOR and p-S6K1 in pancreatic tissue were positively correlated with the pathological scores of pancreatic tissue (r=0.97, P<0.01; r=0.89, P<0.01).ConclusionRapamycin can reduce the degree of pancreatic damage in SAP and has protective effect on pancreatic tissue.