Objective To evaluate the role of monocytic human leukocyte antigen-DR (HLA-DR) and CD16 determinations in inflammatory diseases. Methods A total of 56 patients with inflammatory diseases and 40 healthy subjects (healthy control group) were enrolled for the determinations of HLA-DR and CD16 expression levels [HLA-DR mean fluorescence intensity (MFI) and CD16 MFI],the percentages of positive HLA-DR and CD16 (HLA-DR+% and CD16+%) and MFI (HLA-DR+ MFI and CD16+ MFI) by flow cytometry. The correlations of HLA-DR and CD16 expression levels with neutrophil absolute value(NEUT#),neutrophil percentage(NEUT%),lymphocyte absolute value(LYMPH#),lymphocyte percentage(LYMPH%),monocyte absolute value(MO#),monocyte percentage(MO%)and neutrophil/lymphocyte ratio(NLR) were evaluated. The diagnostic roles of HLA-DR and CD16 in inflammatory diseases were evaluated by receiver operating characteristic (ROC) curve. Results Compared with healthy control group,NEUT#,NEUT%,MO# and NLR in inflammatory disease group were higher(P<0.01),and LYMPH# and LYMPH% were lower (P<0.01). HLA-DR+%,HLA-DR MFI and HLA-DR+ MFI in inflammatory group were lower than those in healthy control group(P<0.01),while CD16 MFI,CD16+% and CD16+ MFI were higher(P<0.01). HLA-DR+%,HLA-DR MFI,HLA-DR+ MFI,CD16 MFI and CD16+ MFI were correlated with NEUT#,NEUT%,LYMPH#,LYMPH%,NLR and MO# (P<0.01),and there was no correlation with MO% (P>0.05). CD16+% was correlated with NEUT#,LYMPH#,LYMPH%,NLR,MO# and MO% (P<0.05),and there was no correlation with NEUT%(P>0.05). ROC curve analysis showed that the areas under ROC curves (AUC) of HLA-DR+%,HLA-DR MFI,HLA-DR+ MFI,CD16+%,CD16 MFI and CD16+ MFI for the diagnosis of inflammatory disease were 0.944,0.944,0.924,0.722,0.911 and 0.979,respectively. Conclusions The determinations of monocytic HLA-DR and CD16 can be used for the diagnosis of inflammatory diseases,and monocytic HLA-DR and CD16 can be used to assess the severity of inflammation and monitor immune status.