Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1beta, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg/mL) for 60 min, thereafter tumor necrosis factor-alpha was added at a concentration of 2.5 ng/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student's t-test where appropriate. Lidocaine (0.5 mg/mL) decreased IL-1beta (1.89 +/- 0.11 versus 4.16 +/- 1.27 pg/mL; P = 0.009), IL-6 (65.5 +/- 5.14 versus 162 +/- 11.5 pg/mL; P < 0.001), and IL-8 (3869 +/- 785 versus 14,961 +/- 406 pg/mL; P < 0.001) concentrations compared with the control. IL-1beta, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg/mL) HUVECs was less than on controls (198 +/- 52.7 versus 298 +/- 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1beta, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.