〔Abstract〕 Objective To explore the effect and mechanism of adenosine A2A receptor(A2AR) on lipopolysaccharide(LPS)-induced inflammatory injury of Caco-2 intestinal epithelial cells. Methods Caco-2 cells were divided into control group, LPS group(treated with 10 μg/ml LPS for 12 h), A2AR agonist(CGS21680) group(pretreated with 50 nmol/L CGS21680 for 10 min), CGS21680+LPS group(pretreated with 50 nmol/L CGS21680 for 10 min, treated with 10 μg/ml LPS for 12 h), cell viability was determined using CCK-8 assay, the secretion levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in cell supernatant of each group were determined using ELISA. mRNA expression levels ofTNF-α,IL-1β and IL-6in cells of each group were detected by real-time fluorescence quantitative PCR, the protein expression levels of microtubule associated light chain protein 3(LC3)-Ⅱ/LC3-Ⅰ and autophagy associated protein(Beclin1) in cells of each group were analyzed using Western blot analysis. Caco-2 cells were then divided into control group, LPS group(pretreated with 50 nmol/L CGS21680 for 10 min), CGS21680+LPS group(pretreated with 50 nmol/L CGS21680 for 10 min, treated with 10 μg/ml LPS for 12 h), CGS21680+LPS+Rapa group(pretreated with 50 nmol/L CGS21680 for 10 min, treated with 10 μg/ml LPS and 5 μmol/L Rapa for 12 h), cell viability was determined using CCK-8 assay, the secretion levels of TNF-α, IL-1β and IL-6 in cell supernatant of each group were determined using ELISA. Results Compared with the control group, the viability of Caco-2 cells in LPS group significantly decreased(P<0.05), the levels of TNF-α, IL-1β and IL-6 in supernatant significantly increased(P<0.05), the mRNA relative expressions ofTNF-α,IL-1β,IL-6in cells significantly increased(P<0.05), the LC3-Ⅱ/LC3-Ⅰ ratio and the relative expression of Beclin1 protein were significantly up-regulated(P<0.05). Compared with LPS group, the viability of Caco-2 cells in CGS21680+LPS group significantly increased(P<0.05), the levels of TNF-α, IL-1β and IL-6 in supernatant significantly decreased(P<0.05), the mRNA relative expression levels ofTNF-α,IL-1β,IL-6in cells were significantly down-regulated(P<0.05), and the ratio of LC3-Ⅱ/LC3-Ⅰ and the relative expression of Beclin1 protein were significantly down-regulated(P<0.05). In addition, compared with CGS21680+LPS group, the viability of Caco-2 cells in CGS21680+LPS+Rapa group significantly decreased(P<0.05), and the levels of TNF-α, IL-1β and IL-6 in the supernatant also significantly increased(P<0.05). Conclusion A2AR agonist can reduce the inflammatory injury of Caco-2 intestinal epithelial cells induced by LPS and improve cell viability, which may be related to its inhibition of autophagy.