Antioxidant system, which is composed of multiple gene families, plays a major role in reducing oxidative damage and xenobiotic detoxification in all living organisms. We identified 50 silkworm antioxidant genes from nine gene families based on the assembled genome sequence. A comparative analysis of the antioxidant genes of the silkworm with other order insects Anopheles gambiae, Apis mellifera, Drosophila melanogaster, and Tribolium castaneum, was performed. We found that most of the antioxidant gene families are highly conserved but Catalase (CAT) and heme-containing peroxidase (HPX) families were lineage-specifically expanded in the silkworm. The expression patterns of the silkworm antioxidant genes were investigated with the known ESTs, microarray data, and reverse transcription-polymerase chain reaction (RT-PCR). Forty two of the 50 silkworm antioxidant genes were transcribed and most of the transcribed genes showed tissue-specific expression patterns. More than a half of lineage-specifically expanded BmCATs lacked 15 or more than 15 of the 36 heme-binding residues and might lose catalase activities. However, the genes encoding these BmCATs showed almost a ubiquitous tissue expression pattern, indicating that they might have evolved new functions. In addition, the lineage-specifically expanded BmHPXs could function in maintaining cell homeostasis in the process of the synthesis of large amounts of silk proteins because they were predominantly expressed in silk gland of the silkworm. The lineage-specific expansion of antioxidant gene families in the silkworm provides useful information for understanding evolution and functional versatility of antioxidant genes in the silkworm even Lepidopteran insects.