Tissue injury in the oral mucosa activates a cascade of transcriptional events important during the healing process that are not yet clearly defined. To characterize these events and identify potential gene targets for future studies, we used cDNA expression arrays in a clinical model of tissue injury. Mucosal biopsies were taken before third molar extraction, 2-4 hours postoperatively, or at 48 hours. Hybridization patterns were analyzed and validated using real-time polymerase chain reaction. Prior to extraction, the biopsied mucosal tissues were characterized by a panoply of genes that were constitutively expressed. After injury, analysis revealed differential expression of genes involved in transcription, inflammation, and remodeling. At 2-4 hours after injury, genes such as Fos, Jun, and early growth response protein were up-regulated, while genes responsible for intercellular adhesion were down-regulated. At 48 hours after injury, the gene profile had shifted toward tissue remodeling. Here we identify genes constitutively expressed in normal oral mucosa and transcriptional events following mucosal tissue injury, which may be useful in identifying new therapeutic targets.