Wound healing in the oral mucosa is clinically distinguished by rapid healing and lack of scar formation compared with dermal wounds. Mechanisms of favorable mucosal healing are yet to be elucidated. Utilizing a murine model of equivalent-size mucosal and skin wounds, we verified the rapid reepithelializaton and reduction in scarring of oral wounds reported in humans. Collagen fibrillar structure in oral wounds rapidly approached the size of normal collagen fibrils, while the collagen ultrastructure in skin remained immature through the later phases of healing. To determine whether the transforming growth factor-beta (TGF-beta) contributes to the lack of scar formation in oral mucosa, we compared the expression and production in oral and skin wounds. The RNase protection assay demonstrated significantly lower levels of TGF-beta1 expression in oral wounds compared with dermal wounds, and no changes were observed in the expression levels of TGF-beta2 or TGF-beta 3. ELISA analysis confirmed that oral wounds contained lower levels of TGF-beta1 levels compared with dermal wounds, along with a significant increase in the ratio of TGF-beta 3 to -beta1. These findings showed reduced scarring in oral wounds at the ultrastructural level, and provide evidence that site-specific differences in TGF-beta production contributes to the superior healing of oral wounds.