This study aimed to characterize the full-length cDNA of thioredoxin-interacting protein (TXNIP) from Megalobrama amblycephala , and investigate its roles in high glucose (HC)-induced inflammatory response. The cDNA obtained covered 2706-bp with an open reading frame of 1203-bp encoding 400 amino acids, compared to Cyprinus carpio , it showed 89.96% homology. The highest expression of txnip was observed in head kidney followed by spleen and liver. After a 12-week feeding trial, high-carbohydrate diet remarkably increased txnip expression in liver and white muscle. Glucose administration resulted in a remarkably increased liver txnip expression, which peaked at 1 h. Thereafter, the expression decreased remarkably to the basal value at 12 h. However, insulin injection resulted in a significant decrease in txnip expression with minimum values attained at 2 h. Subsequently, it gradually increased to the normal values. Moreover, in the in-vitro study, over-expression of txnip along with remarkably increased il-1β and il-6 expression in hepatocytes, and its knockdown led to remarkably reduced il-1β expression. Furthermore, metformin treatment remarkably increased the cell viability and trx expression of hepatocytes under high glucose, while the opposite was true for ROS levels, LDH activity, the ALT/AST ratio, Txnip protein content and the transcriptions of txnip , tnfα and il-1β. • The txnip gene was characterized in an herbivorous fish M. amblycephala. • It shares a high degree of conservation among most fish and higher vertebrates. • Long-term feeding of high-carbohydrate diets increased txnip expression in liver and white muscle. • Glucose load led to a prompt increase of liver txnip expression, whereas the opposite was true after the insulin load. • Metformin alleviated high-glucose induced inflammation in the hepatocytes by TXNIP inhibition. [ABSTRACT FROM AUTHOR]