Objective: To investigate the role of oxidative stress and immunoinflammatory reaction in early stage of diffuse axonal injury (DAI). Methods: 96 adult male SD rats were divided into 2 groups (n = 48 in each): sham group and DAI group. Rat diffuse axonal injury was induced by a rat instant lateral head rotation device, which was developed to let the rat head spin 90 degree at the moment to cause shearing injury. The modified neurological severity score (mNSS), histomorphology, PI staining, GFAP immunofluorescent staining, SOD activity, CAT activity, MDA content and western blotting (IL-6,IL-1, JNK and p-JNK) in parietal cortex were investigated at 6 h, 1 d and 3 d after DAI. Results: The neurological severity scores, GFAP positive cell, PI positive cells, MDA, IL-6, IL-1, JNK and p-JNK were significantly increased and the SOD and CAT activities were decreased after DAI. Conclusion: Oxidative stress and immunoinflammatory reaction played important roles in DAI pathophysiological process in acute phase.