This study aimed to investigate the expression of circular RNA DLGAP4 (circ-DLGAP4) and its correlation with severity, inflammation, inflammatory cytokine levels as well as microRNA-143 (miR-143) expression in acute ischemic stroke (AIS) patients. One hundred and seventy AIS patients and 170 non-AIS controls were enrolled in this study. PBMC and serum from all participants were collected. Circ-DLGAP4 and miR-143 expression in PBMC were detected by qPCR, and TNF-alpha, IL-1 beta, IL-6, IL-8, IL-17 as well as IL-22 expressions in serum were detected by ELISA. The information of CRP, ESR, and National Institutes of Health Stroke Scale (NIHSS) score of AIS patients was collected. PBMC circ-DLGAP4 was down-regulated in AIS patients compared with controls, and ROC curve analysis disclosed that PBMC circ-DLGAP expression had good value in predicting lower AIS risk with area under curve 0.816. Spearman's rank correlation test showed that PBMC circ-DLGAP4 expression negatively correlated with NIHSS score and CRP level in AIS patients. In addition, PBMC circ-DLGAP4 level also was negatively associated with serum expressions of TNF-alpha, IL-6, IL-8 as well as IL-22. Moreover, PBMC circ-DLGAP4 expression was negatively correlated with PBMC miR-143, and PBMC miR-143 was positively associated with NIHSS score, CRP, ESR, TNF-alpha, IL-1 beta, IL-6, IL-8, IL-17, as well as IL-22 levels. Circulating circ-DLGAP4 could serve as a novel biomarker for diagnosis and disease surveillance of AIS and is negatively correlated with inflammation and miR-143 expression in AIS patients.