INTRODUCTION Severe acute pancreatitis (AP) remains a challenge in clinical practice, and there are no internationally agreed specific therapies. Severe AP typically presents with epigastric pain, abdominal distention, vomiting, and constipation at the early stage and is similar to the Yangming-Fushi syndrome of traditional Chinese medicine (TCM). The Chinese herbal ointment Liu-He-Dan (LHD) has been adapted for the treatment of AP with Yangming-Fushi syndrome externally on belly for many years in our hospital. However, the potential mechanism of LHD in the treatment of severe AP has not been elucidated. Therefore, the present study sought to evaluate the effect of LHD on AP patients and preliminarily investigate its anti-inflammatory mechanism.