The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression through a circRNA-miRNA-mRNA network. In our study, microarray was performed to detect the expression profiles of circRNAs during lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Twenty rats were randomly divided into 2 groups, the control group and the LPS group, 10 rats in each group. Three rats each from both groups were randomly selected. Using circRNA microarray data, we compared the circRNA expression profiles in lung tissues between these 6 rats. The most differentially expressed circRNA species from these profiles were validated and optimized as ARDS biomarkers and potential therapeutic targets. Overall, 395 and 562 circRNAs were significantly up- and down-regulated in LPS group vs. control group, respectively. Six up regulated and 4 down-regulated circRNAs from the top 10 candidates were eventually selected to be validated. Among them, only 4 up-regulated circRNAs (mmu_circRNA_19423, rno_circRNA_010489, rno_circRNA_011426, mmu_circRNA_30664) and 1 down-regulated circRNA (rno_circRNA_005564) exhibited significant validation. The 5 highest ranking target miRNAs of these 5 validated circRNAs were predicted according to the miRNA support vector regression method. This is the first study to investigate circRNA expression profile and a large number of aberrantly expressed circRNAs were revealed during ARDS. The significantly over- or under-expressed circRNA may represent a novel biomarker and be developed as a novel therapeutic target for the clinical management of ARDS. The results are preliminary and need to be confirmed in further well-designed studies with larger sample size. (C) 2017 Elsevier Inc. All rights reserved.