Abstract： Objective To investigate the regulating mechanisms of extracellular signal-regulated kinase 1/2 signaling pathway on the neuron apoptosis after diffuse brain injury(DBI) in rats and provide basic of treatment. Method Male Sprague-Dawley rats were randomly divided into four groups: control group, model group, low dose of inhibitor U0126 treatment group and high dose of inhibitor U0126 treatment group. DBI rat model was established according to the description of Marmarou diffused brain injury. The changes of neuron morphous were observed with light microscopy. The level of ERK1/2 phosphorylation and Bax were measured by immunohistochemistry and Western-Blot. Apoptosis was measured with TUNEL method. Results Compared to control group, some neurons displayed histopathologic changes of necrosis. The expression levels of ERKI/2 phosphorylation, Bax and number of apoptotic nerve cell increased (P< 0.05). After treatment with U0126,the ERK1/2 Phosphorylation, Bax expressions and number of apoptotic nerve cell were significantly decreased especially in high dose of U0126 group (P <0.05). Conclusions After DBI ,The activated ERK1/2 signaling pathway plays an important role in process of nerve cell apoptosis by regulating Bax expression.