Abstract: Objective To investigate the effects of tramadol on insulin resistance (IR) during cesarean section complicated with gestational diabetes mellitus (GDM). Methods 120 patients of elective caesarean sectioncomplicated with GDM (level A1) were collected from Dec.2015 to Oct.2016, randomly divided into the tramadol injection treated groups (0.5 mg/kg-TRM1, 1 mg/kg-TRM2 and 1.5 mg/kg-TRM3) and the control group (CON) (n=30). The patients of TRM groups were injected with tramadol after delivery of fetus during caesarean delivery under combined spinal-epidural anaesthesia (CSEA) and the patients of CON group were treated with normal saline as control. The plasma were collected before CSEA (T₀), after delivery of fetus (T₁) and immediately after caesarean section (T₂) for determination of the expression of blood glucose, insulin, HOMA-IR, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by hexokinase,chemiluminescence method and ELISA. The activation of PI3K/Akt signaling pathway of epiploon were detected by RT-PCR and Western blot. Results Compared with T₀, the concentration of blood glucose, insulin, HOMA-IR, IL-6 and TNF-α increased significantly in T₁ and T₂ (P<0.05). The factors of above decreased in T₂ of TRM2 group and TRM3 group comparing with CON group, but of no significant differences between TRM1 group and CON group. Compared with CON group in T₂, PI3K/Akt signaling pathway activated significantly in TRM2 group and TRM3 group (P<0.05). Conclusion The tramadol can attenuate IR during cesarean section complicated with GDM and may regulate the secretion of IL-6, TNF-α and PI3K/Akt signaling pathway in the treatment of IR of GDM.