Alcohol consumption is a major risk factor accelerating the progression of liver disease in patients with chronic hepatitis virus infection. However the mechanism underlying the enhanced susceptibility of alcoholics to liver injury is not fully understood. Here we demonstrate that chronic ethanol consumption significantly increases the susceptibility of C57BL/6N mice to Concanavalin A (Con A)-induced T cell-mediated hepatitis. Injection of a low dose of Con A (5µg/g) caused severe liver damage in ethanol-fed mice as evidenced by a significant elevation of serum ALT levels, massive necrosis, and infiltration of leukocytes, but only slightly induced liver injury in control pair-fed mice. In ethanol-fed mice, the activation and cytotoxicity of NKT cells that play key roles in Con A-induced T cell hepatitis, were not significantly enhanced relative to pair-fed mice. Moreover, Con A-induced activation of hepatic NF-B was significantly increased, whereas activation of STAT1 and STAT3 was attenuated in ethanol-fed mice. Consistent with this result, the expression of chemokines and adhesion molecules (such as ICAM-1, MIP-1, MIP-2, and MCP-1) controlled by NF-B was upregulated, whereas STAT1- controlled expression of chemokines (such as MIG and IP-10) was downregulated in ethanol-fed mice compared to pair-fed mice. In conclusion, chronic alcohol consumption accelerates T cell-mediated hepatitis via upregulation of NF-B signaling pathway and subsequently enhancing expression of chemokines/adhesive molecules and recruitment of leukocytes into the liver.