Background: Hyperglycemia which triggers an increase in oxidative stress can cause inflammation of the liver tissue. This study aims to look at the effect of the ethanol extract of Annona muricata leaves which has a hepato-protective function on liver histopathological changes in mice that have diabetes mellitus. Methods: This study used 25 Swiss Webster mice which were randomly divided into 5 groups: the Negative Control (KN), Positive Control (KP) group, the treatment group dose 150 mg, 300 mg, 600 mg. Histopathological features will be assessed using the NASH CRN score which will then be processed using SPSS version 24 using the Chi-Square test. While blood glucose levels will be tested using the Kruskal-Wallis test with the post hoc Mann Whitney UTest. Results: The results of the ethanol extract of Annona murica leaves in the 5 dose groups showed significant differences in lobular inflammation (p = 0,000) and steatosis (p = 0.001). In this studyalso found a significant relationship between steatosis variables with lobular inflammation (p = 0.535). Conclusion: There is a significant relationship to the ethanol extract of Annona muricata leaves on changes in steatosis and lobular liver inflammation in mice.