CYP2E1 induced oxidative stress plays a central role in the progression of alcoholic liver injury. CYP2E1 can be induced by alcohol consumption and other chemicals such as pyrazole, acetone and isoniazid.  The biochemical and toxicological actions of CYP2E1 have been determined in both constructed human HepG2 cell lines which express CYP2E1 (E47 cells), and in CYP2E1 knockout mice. Ethanol, iron, or polyunsaturated fatty acids were toxic to E47 cells, but not to HepG2 cells without expression of CYP2E1 (C34 cells). This toxicity was associated with enhanced oxidant stress and can be prevented by antioxidants. Liver toxicity was found in mice treated with chronic alcohol, and this toxicity was prevented when CYP2E1 was inhibited or deleted. These data indicate that CYP2E1 plays an important role in hepatotoxicity induced by alcohol and some other stimuli. Applying alcohol or activation of CYP2E1 was shown to increase the activation of JNK and p38 mitogen-activated protein kinase (MAPK), but decreased activation of ERK. These changes in MAPK promoted apoptosis and cell toxicity. In this review, we will address studies on CYP2E1 induced oxidative stress by alcohol, and how MAPK signaling cascades are involved in alcohol induced liver injury.