Objective: To compare the effects of different methods of anesthesia and analgesia on the activities of phosphofructokinase(PFK), glucose-6-phosphate dehydrogenase(G-6PD) and aldose reductase(AR) in erythrocytes and levels of plasma glucose and stress hormones in patients undergoing esophagus surgery. Methods: Sixty-two patients scheduled for esophagus surgery were randomly divided into three groups: groupⅠ(n = 20) receiving only general anesthesia(GA) followed by intravenous patient controlled analgesia(PCA) with fentanyl 15μg/kg. The other two groups receiving both general anesthesia combined with thoracic epidural anesthesia (GEA) and either intravenous PCA with fentanyl 15μg/kg (groupⅡ, n = 21) or thoracic epidural analgesia(TEA) with 0.125% ropivacaine and 0.0002% fentanyl mixture(groupⅢ, n = 21) after the operation. Venous blood samples were collected for measurements of PFK, G-6PD and AR activities in erythrocytes and plasma glucose, cortisol, epinephrine and norepinephrine before induction (T1), 60 min following the incision (T2), 60 min(T3) after operation, on the 1st(T4) and 2nd postoperative day(T5). Results: The activities of PFK decreased(P < 0.01 or P = 0.004) and the activities of G-6PD and AR increased(P < 0. 01) in groupsⅠand Ⅱ on T4 compared with those on T1. Between the two groups, the activities of these enzymes in groupⅡchanged less than those of groupⅠ(P < 0.01 or P < 0.05). These enzymes activities changed slightly in group Ⅲ on T4(P > 0.05). There were significant differences between group Ⅲ and the other two groups(P < 0.01 or P < 0.05). The levels of plasma glucose increased significantly on T2(P < 0.01), reached peak values on T4(P < 0.01) and fell on T5 in the three groups. Compared to those of groupsⅠandⅡ, the values of plasma glucose in group Ⅲ were lower on T4 and T5(P < 0.05 or P < 0.01). The cortisol concentration in each group increased significantly at T2(P < 0.01 or P < 0.05), and remained elevated on T5(P < 0.01 or P < 0.05), while on T2 and T3 the cortisol levels of groupⅠwere higher than that of groupsⅡand Ⅲ(P < 0.05). The levels of group Ⅲwere lower than those of the other groups on T4 and T5(P < 0.01 or P < 0.05). The levels of epinephrine and norepinephrine were also significantly higher in group I than those of the other two groups on T2(P < 0.01 or P < 0.05), and their levels in groupⅠandⅡwere higher than that of group Ⅲ on T4. The patients of the three groups obtained satisfactory pain relief, with all Vidual Analogue Scale(VAS) scores less than 3. VAS scores of groupⅠwere much greater 4h after operation. Group Ⅲ VAS scores were the lowest 24h after operation. However, the number of times patients pressed the bolus switch was higher in groupⅡ(P < 0.01). Conclusion: Compared with GA and intravenous PCA, general anesthesia combined with thoracic epidural anesthesia and analgesia obtain better pain relief and could markedly alleviate the stress response and improve these erythrocyte glucose metabolism changes after esophagus surgery.