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Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.