The present light microscopic investigation was undertaken in order to study the initial phase of orthodontic root resorption in areas of pressure and, more specifically, to focus on the first cells that penetrate the root surface. Twenty-one upper first molars (rats) and 31 lower first molars (mice) were moved mesially by a fixed orthodontic appliance. The experimental periods were 1, 2, 3, 4, and 5 days in rats, and 1, 2, 3, 4, 5, 6, 7, and 8 days in mice. Tartrate-resistant acid phosphatase (TRAP) and Haematoxylin Eosin (H&E) stains were used. Root resorption related to a hyalinized zone showed a consistent pattern: Root resorption started in the circumference of the necrotic hyalinized tissue. In the central parts of the hyalinized zone frontal root resorption occurred 3–4 days later than in the periphery. Indications that the mechanisms for circumferential and central resorption differed was the reason for presenting only the periphery stage in this paper. The initial penetration of cells into precementum/cementum occurred at the peripheries or at a short distance from the peripheries of the hyalinized zone. These cells were TRAP-negative, indicating that they were not clasts or clast precursors. Before this happened TRAP-negative macrophage-like cells were observed at the borderline between the hyalinized tissue and vital periodontal membrane (PM). TRAP-positive cells were first observed in the bone marrow spaces. During the later stages mono- and multi-nucleated TRAP-positive cells were participating in active removal of the hyalinized tissue toward the root surface, and in resorption of cementum and dentine.