The objective of the study was to test for the first time the molecular adaptation of the glucose metabolism to this fish species know to be a good user of carbohydrates. In this way, Nile tilapia were fed with 3 different levels of carbohydrates 0% (CHO-L) 30% (CHO-M) and 50% (CHO-H) dextrin. After 45 days and 90 days of feeding we analyzed the plasma parameters, zootechnical performance and the mRNA levels for genes involved in glycolysis, gluconeogenesis, lipogenesis and glucose transport in liver and muscle. The best growth performance was found for fish fed M-CHO diet, the fish fed with the H-CHO diets showing the worst growth performance. Increased of hepatic and muscle glycogen, hepatic somatic index and plasma metabolites (glucose, triglycerides and cholesterol) was linked to the increased of dietary carbohydrates. However, no hyperglycemia, no change of body compositions was found showing that dietary carbohydrates are efficiently used as an energy source in tilapia. Moreover, in contrats to the dietary protein-linked decreased of amino acid catabolic mRNA levels, no clear molecular adaptation for glycolysis, gluconeogenesis, lipogenesis in liver and glycolysis in muscle was detected except higher mRNA levels for glucose transporter in muscle. Our data suggest that these metabolic pathways at a molecular level are not the main actors explaining the efficient use of glucose in tilapia. Statement of relevance: Our study aimed at characterizing for the first time the molecular effects of increased dietary carbohydrates (dextrin) from 0% up to 50% in Nile tilapia during 45 and 90 days. Our study confirmed that Nile tilapia can use high level of carbohydrates without any deregulation of glucose homeostasis. However, no strong regulations of expression for genes involved in glucose metabolism in liver and muscle - which could explain the reasons for an efficient use of carbohydrate by this fish species - were detected