Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Icariin (ICA), a flavonoid glycoside, has been reported to have several pharmacological effects; however, the anti‑inflammatory effects of ICA against AP require further study. Therefore, we aimed to investigate the effect of ICA on cerulein‑induced AP. In the present study, AP was induced by intraperitoneally administering a supramaximal concentration of cerulein (50 µg/kg/h) for 6 h. ICA was also administered intraperitoneally, and mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to determine serum amylase and lipase levels. The pancreas and lung were rapidly removed for histological examination, and the analysis of myeloperoxidase activity. In addition, reverse transcription‑quantitative polymerase chain reaction was conducted to analyze the expression of inflammatory cytokines in pancreatic tissues. Our results revealed that the administration of ICA prevented an increase in the pancreas weight/body weight ratio of mice and serum digestive enzyme levels. ICA treatment also inhibited cerulein‑induced histological injury and neutrophil infiltration of the pancreas and lung. In addition, ICA suppressed the production of pro‑inflammatory cytokines, including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α in the pancreas. Furthermore, ICA administration was observed to inhibit p38 activation during cerulein‑induced AP. Inhibition of p38 activation resulted in alleviated pancreatitis. Collectively, our results suggested that ICA exhibits anti‑inflammatory effects in cerulein‑induced AP via the inhibition of p38.