Choice of the anesthestic technique can reduce or even eliminate stress responses to surgery and decrease the incidence of complications. Our aim was to compare a combination of epidural anesthesia+general anesthesia with general anesthesia alone as regards perioperative insulin resistance and inflammatory activation among renal transplant recipients. Forty-six nondiabetic patients undergoing renal transplantation were prospectively randomized to the epidural anesthesia + general anesthesia group (n = 21), or general anesthesia alone group (n = 25). Plasma levels of glucose, insulin, interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, resistin, and adiponectin were measured at baseline (T1), end of surgery (T2), postoperative first hour (T3), postoperative second hour (T4) and postoperative 24th hour (T5). Homeostasis model assessment-estimated insulin resistance (HOMA-IR) scores were calculated at every time point that the blood samples were collected. Glucose levels (P < .001) and insulin levels at the end of surgery (P = .048) and at postoperative first hour (P = .005) and HOMA-IR levels at the end of surgery (P = .012) and at postoperative first hour (P = .010) showed significantly higher values among the general anesthesia alone group when compared with the epidural+general anesthesia group. TNF-alpha levels at postoperative 2nd and at 24th hour (P = .005 and P = .004, respectively) and IL-6 levels at postoperative 1st and 2nd hours (P = .002 and P = .045, respectively) were significantly higher in the general anesthesia alone group when compared with the epidural+general anesthesia group. The TNF-alpha levels were significantly less at all time points when compared with baseline only in the epidural+general anesthesia group (T1, 33.36 vs 37.25; T2, 18.45 vs 76.52; T3, 15.18 vs 78.27; T4, 10.75 vs 66.64; T5, 2.98 vs 36.32) Hospital stays were significantly shorter among the epidural+general anesthesia group (P = .022). We showed partly attenuated surgical stress responses among patients undergoing renal transplantation using general anesthesia combined with epidural anesthesia compared with general anesthesia alone.