Abstract: Objective To explore whether β-arrestin2 plays a role by regulating autophagy in colitis. Methods 20 β-arrestin2 wild-type （WT） and 20 β-arrestin2 knockout （KO） mice were randomly and evenly divided into four groups, including β-arrestin2 WT control group and experimental group, β-arrestin2 KO control group and experimental group. In the experimental groups, the mice were given free access to 3% dextran sulfate sodium （DSS） for 7 d to induce acute colitis. In the control groups, the mice were given sterile ddH₂O. The disease activity index of mice was observed and recorded in each group. The colon tissues of mice were collected, and the expression levels of autophagy-related proteins including LC3B and Beclin1 were observed and detected by immunohistochemistry and western blot. The expression of β-arrestin2 was knockdown by siRNA in HCoEpiC cells, and then the cells were treated by Earle’s Balanced Salt Solution （EBSS） to induce autophagy. Then, the expression level of LC3B protein was detected. Results The expression of autophagy-related proteins was significantly up-regulated in the colon mucosal tissues of WT experimental mice. Compared with WT mice, the colonic inflammation was significantly ameliorated in β-arrestin2 KO mice after DSS treatment. And the expression levels of autophagy-related proteins LC3B-Ⅱ/Ⅰ were significantly down-regulated in β-arrestin2 KO mice in the experimental groups（P < 0.05）.There is no significant difference in the expression levels of Beclin1（P > 0.05）. After knocking down the expression of β-arrestin2 in HCoEpiC cells and EBSS treatment, the expression levels of LC3B-Ⅱ/Ⅰ were significantly down-regulated （P < 0.05）. Conclusion β-arrestin2 can regulate the autophagy in colitis, and the deficiency of β-arrestin2 can inhibit autophagy to ameliorate the colonic inflammation.