Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causedby progressive loss of motor neurons in the brainstem and spinal cord.(-)-epigallocatechin-3-gallate, a major constituent of green tea, is reported to possesspotent iron-chelating, radical-scavenging , anti-inflammatory and anti-apoptosisactivities, which may provide neuronal protection. The purpose of our study is toevaluate neuroprotective effect of EGCG in transgenic mouse model of ALS.SOD1-G93A mice and wild-type mice were randomly divided into EGCG-treatedgroups (10mg/kg, p.o) and vehicle-treated control groups. Rotarod measurement wasperformed to assess the motor function of mice started at the age of 70 days. Nisslstainning to examine the number of motor neurons and CD11b and GFAPimmunohistochemical staining to evaluate activation of microglial and astrocytes inthe lumber spinal cords were conducted at the age of 120 days. In addition, for furtherobservation of regulation of cell signal pathway by EGCG, we usedimmunohistochemical analysis for NF-κB and cleaved caspased-3 as well as westernblot to determine the expression of inducible nitric oxide synthase (iNOS) and NF-κBin the spinal cord.Our study demonstrated that orally administration of EGCG beginning frompre-symptomatic stage significantly delayed the onset of disease, and extended lifespan for two weeks. Furthermore, EGCG-treated transgenic mice showed diminishedmicroglia and astrocytes activation in spinal cord, reduced immunohistochemicalreaction of nuclear factor kappa B (NF-κB) and cleaved caspased-3 as well as proteinlevel of iNOS and NF-κB.In conclusion, the results provide further evidences that EGCG hasmultifunctional therapeutic effects benefit for the mouse model of ALS.