Objective To explore the protective effect of brain-derived neurotrophic factor (BDNF) on cultured rat cortical neurons against glutamate (Glu)-induced injury and its mechanism. Methods Cortical neurons were primarily cultured from 1-day-old newborn Sprague-Dawley rats and then cultured for 7 d. The cortical neurons were divided randomly into 3 groups: control group,Glu group and BDNF group after identified with neuron-specific enolase (NSE) immunostaining. The cells of BDNF were treated with 50 ng/ml BDNF on day 6 for 24 h followed by cultured with 50 ?mol/L Glu for 0.5 h. While,the cells of Glu group were cultured with 50 ?mol/L Glu for 0.5 h on day 7. The control cells received no such treatments. On day 8,cell viability were determined by the colorimetric MTT assay. The morphological features of the neuron cells were observed under AO/EB fluorescence microscopy. Expressions of p75NTR,JNK and ERK were observed using Western blot analysis. Results On day 8,the primary cortical neurons grew well. BDNF protected cortical neural cells from Glu injury. Cell viability of BDNF group was (1.14?0.06),significantly higher than that of Glu group (0.72?0.10,P