In Drosophila, the fat body is a collective name for the masses and sheets of adipose tissue that are distributed throughout the fly body. Thus far, >386, 000 Drosophila expressed sequence tags (ESTs) have been deposited to the GenBank database, including 10, 443 derived from fat body in flies (data accessed on October 7, 2004). The objective of this study was to map the transcriptome of the fat body in flies and thus provide genomics and bioinformatics tools for developing a Drosophila model for addressing the genetic complexity of obesity in humans. The gene—EST Basic Local Alignment Search Tool (BLAST) matches revealed that these ESTs could represent 12, 188 coding genes in the Drosophila genome. Among them, at least 2261 are expressed in the fat body, including 41 identified as preferentially expressed genes with logarithm of odds >3.0. Self-organizing map analysis revealed a cluster of 290 genes favorably expressed in the fat body compared with genes expressed in five other tissues. Mapping of the fat body transcriptome identified a 1.7-Mb domain on 3L containing 35 genes that were expressed at a much higher level than in other tissues (transcript density factor = 1.0 ∼ 2.3).