Objective：To investigate the effect of urantide，a urotensin Ⅱ receptor antagonist，on the phosphorylation of signal transducers and activators of transcription（STAT3）expression in the fatty liver of atherosclerosis（AS） rats. Methods：A total of 30 male Wistar rats were randomly divided into three groups：control group，AS group and Urantide group. The AS group and Urantide group were induced by an intraperitoneal injection of vitamin D3（VD3）150 μg/（kg·d）for 3 days and by feeding with special high fat food. Following successful modeling，the Urantide group was given urantide 30 μg/（kg·d）for 2 weeks by tail vein injection. The body weight and liver weight of each rat were measured to calculate the liver index. HE staining was used to observe the morphological change of the thoracic aortae and livers of the rats. Biochemical indexes were measured by detecting the change of alanine transaminase（ALT）and aspartate aminotransferase（AST）in the serum of rats. The expression levels of STAT3 mRNA in liver tissues were detected by RT-qPCR. The levels of STAT3 and p-STAT3 protein in liver tissues were detected by Western blot. Immunofluorescence was used to detect the levels of p-STAT3 in the hepatocytes of each group. Results：Compared with the control group，the HE staining of the AS group showed typical AS pathological change of thoracic aortae and typical steatosis of the livers；the liver indexes，the levels of ALT，AST in the serum and the level of p-STAT3 in the livers increased significantly in the AS group. Compared with the AS group，the AS pathological changes and the steatosis of the livers in the Urantide group were significantly alleviated；the liver indexes，the levels of ALT，AST in the serum and the level of p-STAT3 in the livers decreased significantly in the Urantide group. In addition，no significant changes were observed in the expression levels of STAT3 mRNA and protein in the liver tissues of each group. Conclusion：Urantide can alleviate liver injury by inhibiting the activation of STAT3 in the treatment of fatty liver.