To explore the therapeutic effect of vascular softening pills on non-alcoholic fatty liver disease(NAFLD) mice.Methods:The C57BL/6 mice were taken as the normal group(n=10).The NAFLD model was constructed by feeding apolipoprotein E-deficient(ApoE-/-) mice with a high-fat diet for 18 weeks.The successfully modeled mice were divided by the random number table method into the following 6 groups：a model group，a low-dose vascular softening pill group，a high-dose vascular softening pill group，an atorvastatin group，a joint treatment group，and an inhibitor group，with 10 mice in each group.The normal group and model group were administered saline of 10 mL/(kg·d) by gavage.The low-and high-dose vascular softening pill groups were administered vascular softening pills of 2.34 and 4.68 g/(kg·d) by gavage，respectively.The atorvastatin group was administered atorvastatin calcium tablets of 10 mg/(kg·d) by gavage.The joint treatment group was administered vascular softening pills of 4.68 g/(kg·d) by gavage and AMP-activated protein kinase(AMPK) inhibitor Compound C 10 mg/(kg·d) by intraperitoneal injection.The inhibitor group was administered Compound C 10 mg/(kg·d) by intraperitoneal injection.The above intervention was given once a day for 6 continuous weeks.Afterward，the following indices of blood lipid and liver function were determined in each group：triacylglycerol(TG)，total cholesterol(TC)，low-density lipoprotein cholesterol(LDL-C)，high-density lipoprotein cholesterol(HDL-C)，alanine aminotransferase(GPT)，and aspartate aminotransferase(GOT).Hematoxylin-eosin(HE)，Masson，and oil-red O staining were conducted to observe pathological changes in liver tissues.Enzyme-linked immunosorbent assay(ELISA) was performed to determine liver interleukin-1β(IL-1β) and IL-18 levels.Western blot was employed to determine the expression of AMPK，p-AMPK，and NOD-like receptor thermalprotein structural domain-associated protein 3(NLRP3) in liver tissue.Immunofluorescence double(IF) staining was utilized to determine AMPK and NLRP3 expression in liver tissue.Results:Compared with the model group，blood lipid disorder was improved in the high-dose vascular softening pill group and atorvastatin group，with decreased GPT，GOT，IL-1 β，and IL-18 levels，reduced liver cell swelling，decreased fat vacuoles and lipid deposition，increased expression levels of liver p-AMPK protein，and decreased NLRP3 protein expression levels(P<0.05).Compared with the joint treatment group，blood lipid disorder and liver injury were improved in the high-dose vascular softening pill group，with reduced pathological morphological changes in hepatocytes，reduced liver IL-1β and IL-18 levels，reduced NLRP3 protein expression in liver tissue，and increased p-AMPK expression，while the opposite condition occurred in the inhibitor group.Conclusion:Vascular softening pills effectively protect NAFLD mice by improving liver lipid deposition and inflammatory response，which might be relevant to its regulation of the AMPK/NLRP3 signaling pathway.