Objectives: High expression of MMP-2 and MMP-9 in periapical lesions plays an important role in the degradation of the extracellular matrix. This study aimed to investigate the effect of epigallocatechin-3-gallate (EGCG)-based endodontic paste as an intracanal dressing on the expression of MMP-2 and MMP-9 in periapical lesions. Materials and Methodss: Periapical lesions were experimentally induced in 35 mature beagle dog premolars randomly divided into healthy teeth, untreated periapical lesions, periapical lesionstreated in a single session, and periapical lesions treated in two sessions with EGCG or calcium hydroxide-based pastes. The operator monitored the animals and performed euthanasia after 120 days for histopathologic and immunofluorescence analyses to assess the expression of MMP-2 and MMP-9. Then we perform the statistical analysis. Results: Endodontic treatment in two sessions using EGCG and calcium hydroxide-based pastes provided similar levels of repair of the apical and periapical tissues and neoformation of periodontal ligament fibers, cementum and alveolar bone. In both groups, the expression of MMP-2 and MMP-9 was minimal,and it was observed in the cytoplasm of fibroblasts, osteoblasts, cementoblasts, cementocytes and vascular endothelium. In healthy teeth, the expression of MMPs was minimal and was found in odontoblasts. Endodontic treatment in a single session did not result in full repair of periapical lesions, and they presented intense expression of MMP-2 and MMP-9, including in the cytoplasm of persistent inflammatory cells, similar to untreated lesions. In both groups treated in two sessions, the expression of MMP-2 and MMP-9 was similar to that in healthy teeth, and it was significantly lower than that in periapical lesions treated in a single session or untreated (p <0.001). Conclusions: The use of EGCG-based endodontic paste reduced the expression of MMP-2 and MMP-9 and allowed for the repair of periapical lesions, similar to calcium hydroxide-based paste, and it was superior to treatment performed in a single session. Clinical Relevance: This study was the first one that evaluated the use of EGCG- based paste as intracanal treatment resulted in a reduction of the expression of MMPs 2 and 9 and repair of periapical lesions, similarly to calcium hydroxide-based paste.