A humanized antibody specifically binding to an amino acid sequence (EEEDDDDE (SEQ ID NO: 60)) present in the C-terminal domain of High Mobility Group Box 1 (HMGB1) protein, or an antigen-binding fragment thereof, which is capable of neutralizing the biological activity of HMGB1 protein, comprising a heavy chain variable region and a light chain variable region, wherein (i) the heavy chain variable region comprises: (a) an amino acid sequence of heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 7, (b) an amino acid sequence of heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and (c) an amino acid sequence of heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9, and (ii) the light chain variable region comprises: (a) an amino acid sequence of light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, (b) an amino acid sequence of light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and (c) an amino acid sequence of light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein (iii) the heavy chain variable region comprises the amino acid sequences of SEQ ID NOs: 43, 44, 45 and 46 as amino acid sequences of FR1, FR2, FR3 and FR4, respectively, wherein the amino acid sequences of FR1, FR2, FR3 and FR4 optionally have mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequences of SEQ ID NOs: 43, 44, 45 and 46, respectively, and (iv) the light chain variable region comprises the amino acid sequences of SEQ ID NOs: 47, 48, 49 and 50 as amino acid sequences of FR1, FR2, FR3 and FR4, respectively, wherein the amino acid sequences of FR1, FR2, FR3 and FR4 optionally have mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequences of SEQ ID NOs: 47, 48, 49 and 50, respectively, wherein (v) the heavy chain variable region comprises an amino acid sequence in which the amino acid residues at positions 49 and 94 are alanine, and (vi) the light chain variable region comprises an amino acid sequence in which the amino acid residues at positions 44 and 46 are isoleucine and arginine, respectively, and wherein the binding activity of the humanized antibody to human HMGB1 protein, analyzed by ELISA assay, is 2-fold or higher than that of #10-22 chimeric antibody when compared at 250 ng/ml, wherein the #10-22 chimeric antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 13 and a light chain having the amino acid sequence of SEQ ID NO: 14. (i) the heavy chain variable region comprises: (a) an amino acid sequence of heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 7, (b) an amino acid sequence of heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and (c) an amino acid sequence of heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9, and (a) an amino acid sequence of heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 7, (b) an amino acid sequence of heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and (c) an amino acid sequence of heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9, and (ii) the light chain variable region comprises: (a) an amino acid sequence of light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, (b) an amino acid sequence of light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and (c) an amino acid sequence of light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein (a) an amino acid sequence of light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, (b) an amino acid sequence of light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and (c) an amino acid sequence of light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein (iii) the heavy chain variable region comprises the amino acid sequences of SEQ ID NOs: 43, 44, 45 and 46 as amino acid sequences of FR1, FR2, FR3 and FR4, respectively, wherein the amino acid sequences of FR1, FR2, FR3 and FR4 optionally have mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequences of SEQ ID NOs: 43, 44, 45 and 46, respectively, and (iv) the light chain variable region comprises the amino acid sequences of SEQ ID NOs: 47, 48, 49 and 50 as amino acid sequences of FR1, FR2, FR3 and FR4, respectively, wherein the amino acid sequences of FR1, FR2, FR3 and FR4 optionally have mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequences of SEQ ID NOs: 47, 48, 49 and 50, respectively, wherein (v) the heavy chain variable region comprises an amino acid sequence in which the amino acid residues at positions 49 and 94 are alanine, and (vi) the light chain variable region comprises an amino acid sequence in which the amino acid residues at positions 44 and 46 are isoleucine and arginine, respectively, and wherein