Circulating microRNAs have the potential to be noninvasive biomarkers for assessing disease progression. MicroRNA-551b-5p (miR-551b-5p) was previously reported to be differentially expressed in pancreatic patients. The serum miR-551b-5p level was measured in patients with mild acute pancreatitis (MAP), severe acute pancreatitis (SAP), and healthy controls using quantitative real-time polymerase chain reaction (RT-PCR) analysis to evaluate its impact on inflammatory response. Acute Physiology and Chronic Health Evaluation II (APACHE II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Assessment Score (SOFA), and Ranson's scores were recorded. Inflammatory cytokines, IL-6, IL-17, IL-1β, and Tumor Necrosis Factor-α (TNF-α), were detected in serum samples obtained from MAP and SAP patients on admission day 1, day 3, and day 5 using Enzyme Linked Immunosorbent Assay (ELISA). Inflammatory cytokines were analyzed in peripheral blood mononuclear cells (PBMCs), which were transfected with miR-551b-5p-negative controls and inhibitors. The serum miR-551b-5p level was significantly higher in MAP and SAP patients compared to controls (P < 0.001). An elevated miR-551b-5p level is positively associated with APACHE II, MODS, SOFA, and Ranson's scores (P < 0.001). Serum cytokines levels were significantly elevated in MAP and SAP patients compared to controls (P < 0.05). In addition, the level of these inflammatory cytokines was increased in PBMCs of SAP patients in comparison with those of healthy controls (P < 0.05), and this rise was significantly reduced with the addition of an miR-551b-5p inhibitor. In conclusion, serum miR-551b-5p is elevated in patients with MAP and SAP and is involved in the regulation of inflammatory response. It may be a useful biomarker for assessing the severity of SAP.