Abstract： Objective： To discuss the effect of Schizandrin B(Sch B) regulating miR- 22- 3p/runt- related transcription factor 3(RUNX3) molecular axis on injury of acinar cells with severe acute pancreatitis(SAP). Methods： The pancreatic acinar cells AR42J of rats were divided into the Con group，the SAP group，the SAP + Sch- L group，the SAP + Sch-M group，the SAP+Sch-H group，the SAP+anti-miR-NC group，the SAP+anti-miR-22-3p group，the SAP+Sch+miR-NC group，and the SAP+Sch+miR-22-3p group. Except for the Con group，the other groups were given caerulein at a dose of 10 nmol/L and lipopolysaccharide at a dose of 10 mg/L to stimulate AR42J cells for 24 hours to establish SAP cell model. In the SAP+Sch-L group，the SAP+Sch-M group，and the SAP+Sch-H group，the cells were treated with Sch B at concentrations of 10，20，and 40 μmol/L; in the SAP+anti-miR-NC group and the SAP+anti-miR-22-3p group，the cells were transfected with anti-miR-NC and anti-miR-22-3p respectively; in the SAP+Sch+miR-NC group and the SAP+ Sch+miR-22-3p group，the cells were transfected with miR-NC and miR-22-3p mimics respectively and intervened with Sch B at a concentration of 40 μmol/L. The expression levels of interleukin- 6(IL-6) and tumor necrosis factor α(TNF-α) in the culture supernatant of cells were detected by enzyme linked immunosorbent assay. The rate of cell apoptosis was detected by flow cytometry. The mRNA expression levels of miR- 22- 3p and RUNX3 were detected by real- time fluorescence quantitative PCR. The expression levels of RUNX3，B- cell lymphoma- 2(Bcl- 2)，Bcl- 2- associated X protein (Bax)，and cleaved-cysteinyl aspartate specific proteinase 3(cleaved-caspase3) were detected by BCA method. The targeted binding relationship between miR- 22- 3p and RUNX3 was detected by dual- luciferase reporter assay. Results：Compared with those in the Con group，in the SAP group，the expression levels of IL-6，TNF-α，miR-22-3p，Bax，and cleavedcaspase3 in AR42J cells as well as the rate of cell apoptosis were increased(P＜0.05)，and the expression levels of RUNX3 and Bcl- 2 were decreased(P＜0.05). Compared with those in the SAP group， in the SAP + Sch- L group， SAP + Sch- M group and SAP+Sch-H group，the expression levels of IL-6，TNF- α，miR-22-3p and Bcl-2 were decreased(P＜0.05)， and the expression levels of Bax，cleaved- caspase3，and RUNX3 as well as the rate of cell apoptosis were increased(P＜ 0.05)，and in a dose-dependent manner(P＜0.05). Compared with those in the SAP+anti-miR-NC group，in the SAP+antimiR- 22-3p group，the expression levels of IL- 6，TNF-α，and Bcl-2 were decreased(P＜0.05)；the expression levels of Bax，cleaved-caspase3，and RUNX3 as well as the rate of cell apoptosis were increased(P＜0.05). Compared with those in the SAP+Sch+miR-NC group，in the SAP+Sch+miR-22-3p group，the expression levels of IL-6，TNF-α，and Bcl-2 were increased(P＜0.05)；the expression levels of Bax，cleaved-caspase3，and RUNX3 as well as the rate of cell apoptosis were decreased(P＜0.05). Conclusion：Sch B can relieve the injury of acinar cells with SAP by down-regulating miR-22-3p/RUNX3 molecular axis.