AIMS: To investigate the mechanism by which curcumin inhibits pancreatic steatosis (PS), and the diagnostic value of ultrasonography in the pancreas of mice with obesity. MATERIALS AND METHODS: Male mice were randomly divided into normal chow diet (NC), high-fat diet (HFD), and HFD + 80 mg/kg curcumin groups (HC) and maintained for 12 weeks to induce PS. Weight and fasting blood glucose (FBG) were collected biweekly and oral glucose tolerance test and insulin levels were measured in the final week. The morphology and fat infiltration of pancreas were observed by ultrasonography and histology. The level of blood lipid was detected, and the expression of genes and proteins related to lipid metabolism in pancreatic tissues was analyzed. RESULTS: Compared to the NC and HC groups, the HFD group had higher body weight, cholesterol, triglycerides, and LDL and HDL levels, along with increased inflammation and fat deposits in the pancreas. The HC group had milder inflammation and lower glucose intolerance and insulin resistance (P<
0.05). The gray value, steatosis scores, immunohistochemical results, and ORO staining were significantly correlated (P<
0.05). Correlations were found between gray values, steatosis scores, and ORO staining (P<
0.05). In comparison to the HFD, expression of LATS2, FAS, YAP, and SREBP2 were downregulated and p53 was upregulated in the HC group. CONCLUSION: Curcumin is a potential modulator of insulin resistance and SREBP2 expression, with its underlying mechanism possibly mediated through the YAP/p53 signaling pathway. Pancreatic steatosis exhibits distinct ultrasonographic features, making ultrasound an effective diagnostic tool for identifying the condition.