Abstract The effects of dietary sucrose and systemic glucocorticoid treatment on the response of the pulpodentinal complex to dental caries were examined in an experimental rat model. The possible role of dentinal caries on dentin formation was also examined. After 5-6 weeks of a dietary and/or medication period, the areas of dentin formation and dentinal caries were quantified in the molars of growing animals. Also the number and severity of caries lesions were estimated. The 43% sucrose diet significantly reduced dentin formation and increased dentinal caries progression. Although glucocorticoid medication alone reduced dentin formation, without dietary sucrose it did not have an effect on caries. In combination of these two, glucocorticoids further increased the progression of dentinal caries, however without significant increase in the number of caries lesions. The cariogenic bacterial inoculation of rats fed a sucrose or control diet increased the progression of dentinal caries. The relationship between cariogenic bacteria and caries was not strong, but there was a stronger relationship between the total amount of dietary sucrose and dentinal caries. In addition to the overall reduction of dentin formation there was no difference in the amount of dentin formed between intact and carious fissures in the sucrose diet group. On the contrary, rats receiving the control diet positively responded to the dentinal caries by increasing dentin formation to prevent pulpal exposure. Whereas the high sucrose diet impaired both the deposition and mineralization of the dentin matrix, glucocorticoids affected matrix formation only. These results indicate that the functional alterations in the pulpo-dentinal complex might contribute to dentinal caries progression in a cariogenic environment, irrespective of the causative mechanism.