In adhesive restorations, one major problem is hybrid layer degradation. At present, this deterioration is explained by the activation of the endogenous matrix metalloproteinases (MMPs) present in dentin due to the acidic property of adhesive systems. We hypothesized that self-etching adhesive should also stimulate the expression of MMPs in odontoblasts. In cultured tooth slices, we evaluated the changes in MMP-2 and proMMP-9 expression in the dentin-pulp complex after self-etching adhesive treatment on dentin cavities in immunochemistry and by zymography. The treatment resulted in increased MMP-2 expression in odontoblasts, as shown by immunohistochemistry. Zymography showed increased proMMP-9 and MMP-2 in dentin under self-etching treatment when pulp was present. These results showed that self-etching adhesive stimulates the secretion of MMPs from the dentin-pulp complex and, more precisely, by odontoblasts, suggesting that odontoblasts participate in hybrid layer degradation.