This study examined the selected hormonal responses to, and hormone-mediated glucose metabolism during minimally invasive surgery in, patients undergoing laparoscopic cholecystectomy for symptomatic gallstone disease. Thirty-two patients with symptomatic gallstone disease were included in this study and scheduled for open or laparoscopic procedure in a randomized trial. Results are expressed as mean and standard error of the mean. Statistical evaluations were performed with Mann-Whitney U and Wilcoxon signed-rank tests. Blood cortisol, glucagon, insulin, and glucose concentrations were measured immediately in the preoperative period and 6 h after surgery. Blood cortisol, glucagon, and glucose concentrations increased significantly after open and minimally invasive surgery, while insulin levels and the insulin:glucagon ratio remained unchanged. The rise of glucagon and cortisol values was found to be significantly higher in the postoperative period of the open procedure, than in the laparoscopic approach. However, in the patients who underwent open surgery, the increase in glucose concentrations was not significantly higher in the postoperative period. Surgery-induced hormonal effects on the islets increase glucagon and suppress insulin secretion. The glucagon-mediated increase in hepatic glucose production is excluded by the posttraumatic insulin levels from the insulin-sensitive tissues. A bihormonal setting favors a greater rate of hepatic glucose production in both open and laparoscopic surgery. Hormonal changes do reflect the degree of surgical stress, but their metabolic consequences are not parallel to the grade of surgical trauma in minimally invasive surgery.