The aims of this study were to examine the anti-inflammatory effect of curcumin on concanavalin A (ConA) induced hepatitis in mice, and to elucidate its underlying molecular mechanisms. Mice received curcumin by gavage before ConA intravenous administration. The results showed that curcumin pretreatment attenuated ConA-induced hepatitis. Enzyme linked immunosorbent assay (ELISA) results showed that serum levels of high mobility group box 1 (HMGB1) increased at 4 h and reached its peak value at 12 h after challenge with ConA; but this increase was significantly inhibited by curcumin. Furthermore, curcumin significantly decreased the HMGB1 translocation from nucleus to cytoplasm of hepatocytes in ConA-induced mice. The levels of HMGB1 mRNA and protein expression in the liver were also significantly lowered in curcumin-treated mice. In addition, curcumin inhibited intrahepatic expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 protein. In conclusion, the results indicated that curcumin protected against ConA-induced hepatitis in mice; and the beneficial effects may be partly through inhibition of HMGB1 translocation in hepatocytes, release into the plasma and expression in livers.