We have generated a humanized mouse model expressing human VSIG4 in place of the murine counterpart. mRNA and protein expression of human VSIG4 indicates successful generation of the humanized model. Humanization of VSIG4 does not change the overall development, differentiation or distribution of immune cell types in spleen, lymph node and blood. Anti-VSIG4 antibody treatment reduced tumor growth in B-VSIG4 mice, indicating that B-VSIG4 mice are a powerful model for evaluation of anti-human VSIG4 antibodies.