Objective: To study the effect of nerve stimulator-guided nerve block on the pain mediator secretion and stress degree after lower extremity operation. Methods: Patients who underwent lower extremity operation in Mianyang Orthopaedic Hospital between March 2015 and August 2017 were selected, and the analgesia methods within the medical records were reviewed and used to divide the patients into 3 groups:nerve block group, spinal analgesia group and intravenous analgesia group. The secretion of pain mediators, stress hormones, stress products and inflammatory factors in serum was measured 24 hours after surgery. Results:CGRP, β-EP, 5-HT, HA, ACTH, Cor, PRL, GH, TSH, sTNFR-1, IL-2, IL-10 and TGF-β1 secretion as well as CRP, MPO, MDA and ROS generation in serum of nerve block group were significantly lower than those of spinal analgesia group and intravenous analgesia group (P<0.05), and the differences in serum pain mediators, stress hormones, stress products and inflammatory factors were statistically significant between nerve block group and spinal analgesia group as well as between nerve block group and intravenous analgesia group (P<0.05). Conclusion: The nerve stimulator-guided nerve block can be more effective than spinal analgesia and intravenous analgesia to reduce the secretion of pain mediators and relieve the degree of stress after lower extremity operation.