Odontoblasts are postmitotic cells that differentiate from the dental papilla. These cells are responsible for producing the calcified dentin matrix. The pulp-odontoblast interphase contains undifferentiated mesenchymal stem cells, which have the ability to cytodifferentiate into odontoblast-like cells in response to specific signaling molecules. Dentin matrix protein 1 (DMP1) is one of the dentin noncollagenous extracellular matrix proteins that has been implicated in regulation of mineralization. In this study, we have examined the potential role of DMP1 in inducing cytodifferentiation of dental pulp stem cells into odontoblast-like cells and formation of reparative dentin in a rat model. Cavities were drilled and pulps exposed in maxillary first molars. Collagen matrix impregnated with recombinant DMP1 was implanted directly in Group 1, while calcium hydroxide, a commonly used pulp-capping agent was implanted in group 2, collagen matrix that was not impregnated with rDMP1 was implanted directly in group 3, which served as control. Each of these three groups was subdivided into two subgroups, A for 2 weeks time duration and B for 4 weeks duration. At the end of the time period the maxillae were excised, tissues were processed for histological and immunohistochemical evaluations. The results showed that DMP1 could act as a morphogen on undifferentiated mesenchymal cells present in the dentin-pulp complex. These differentiated cells had the potential to regenerate dentin-like tissue, which was confirmed by the presence of collagenous matrix, odontoblast specific markers and calcified deposits. Gene Therapy (2006) 13, 611-620.