Acute pancreatitis (AP) is known worldwide as one of the most common gastrointestinal diseases, prospectively leading to hospitalization coupled with increasing incidence. Several microRNAs (miRNAs) have been reported to be potential biomarkers for pancreatitis. In this study, we verified the hypothesis that miR-92a-3p is implicated in the development of AP by controlling the proliferation and apoptosis of pancreatic acinar cells (PACs) through the modulation of the Kruppel-like factor 2 (KLF2) and inflammatory factors in rats. Initially, we established a rat model of AP and extracted the pancreatic tissues. Then, the positive rate of KLF2 was measured using immunohistochemistry, and the expression of the related genes was determined by rReverse transcription quantitative polymerase chain reaction and Western blot analysis. The cell proliferation and apoptosis were measured by 5-ethynyl-2 '-deoxyuridine assay and flow cytometry, and the contents of inflammatory factors were measured using enzyme-linked immunosorbent assay. AP rats presented with increased miR-92a-3p expression as well as decreased KLF2 expression in PACs. The downregulation of miR-92a-3p and overexpression of KLF2 led to decline in expression of nuclear factor-kappa B (NF-kappa B), survivin, tumor necrosis factor-alpha, and Bax as well as extent of NF-kappa B phosphorylation, contents of inflammatory factors, and apoptosis rate of PACs, but to increased KLF2 and B-cell lymphoma-2 levels and proliferation rate of PACs. Collectively, the data obtained from the present study demonstrated that reduced miR-92a-3p expression may relieve AP through its suppressive effects on cell apoptosis, inflammatory factors, and facilitatory effects on cell proliferation by enhancing KLF2 expression.