Immunoglobulin superfamily (IgSF) proteins are known for their abilities to specifically recognize and adhere to cells. In this paper, we predicted the presence of 133 IgSF proteins in the silkworm (Bombyx mori) genome. Comparison with similar proteins in other model organisms (Caenorhabditis elegans, Drosophila melanogaster, Anopheles gambiae, Apis mellifera and Homo sapiens) indicated that IgSF proteins are conserved but have rapidly evolved from worms to human beings. However, these proteins are well conserved amongst insects. Silkworm microarray-based expression data showed tissue expression of 57 IgSF genes and microbe-induced differential expression of 37 genes. Based on the expression data, we can conclude that the silkworm IgSF is active.