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BACKGROUND To explore the effects of dexmedetomidine on glucose-related hormones and lactate levels in non-diabetic patients undergoing malignant gastrointestinal tumor radical resection. METHODS Groups D1 and D2 received dexmedetomidine loading dose 1 μg/kg and maintenance dose 0.25 and 0.5 μg/kg/h, respectively. Group C received saline solution. Glucose, lactate, insulin, glucagon, cortisol, epinephrine, norepinephrine and dopamine levels were measured before dexmedetomidine infusion (T1), 1 h after surgery beginning (T2), at surgery ending (T3), and 1 h after transfer to the post-anesthesia care unit (T4). RESULTS Compared with group C, glucose levels increased in group D2 at T2 and reduced in groups D1 and D2 at T4. Lactate levels reduced in groups D1 and D2 at T4. A positive correlation between glucose and lactate levels was found in all groups. Compared with group C, insulin level reduced in group D2 at T2; glucagon levels reduced in groups D1 and D2 at T4; cortisol levels reduced in group D1 at T4 and in group D2 at T3 and T4; epinephrine and norepinephrine levels reduced in group D1 at T4 and in group D2 at T2 and T4; and dopamine level reduced in group D2 at T4. CONCLUSIONS Dexmedetomidine loading dose 1 μg/kg and maintenance dose 0.25 μg/kg/h produces a stable insulin level and significant postoperative decreases in glucagon, cortisol, epinephrine and norepinephrine secretion with stable maintenance of intraoperative and postoperative blood glucose levels and decreased postoperative lactate levels in non-diabetic patients under general anesthesia.