Sugars acting as fuel energy or as signaling molecules play important roles in plant growth and development. Although sugars associated with early seedling development have been analyzed in detail, few studies have examined the effect of sugar on genome-wide gene transcription. To analyze the role of glucose on the genomic level, we examined the response of seedlings to 5% glucose using RNA-seq technology. High concentrations of glucose significately altered the expression of 863 genes, with 558 upregulated and 305 downregulated genes by more than 2-fold. A large number of genes affected by glucose were involved in metabolic processes and signaling. Transcript levels for many kinases and calcium signals were downregulated. Most transcription factors identified were also involved in glucose signaling. Moreover, many genes related to the auxin, gibberellin, and abscisic acid responses were upregulated or downregulated. Additionally, the K(+), Ca(2+), SO3(-), NO3(-), PO4(3-), amino acid, and sugar transporters were also upregulated or downregulated. These results provide a basic understanding of the glucose-mediated molecular mechanisms in the regulation of early seedling development.