Objectives: to analyze the healing dynamics of a critically large rat calvarial defect after the application of the new biomaterial of animal origin Cerabone with magnesium, in comparison to the commercial animal biomaterial Cerabone, its mixture with autologous bone, devitalized dentin and autologous rat dentin. Materials and methods: Rat calvarial bone tissue and serum were analysed. Expression of inflammatory, protective and osteoinductive factors and their intracellular messenger molecules was determined by immunohistochemistry. Bone remodeling markers, inflammatory and protective cytocines were determined by ELISA. 2D parameters of bone tissue was determined by histomorphometry, while #D parameters were determined by micro-CT. Quantitative analysis of macrophages was done by double immunofluorescence. Expression of RUNX-2, OC, SOST and RANK were determined by RT-PCR. Results were statisticaly analysed with parametric and non-parametric tests. Statistical significance was set at p<0,05. Results: bone volume was measured by micro-CT and histomorphometry increase with increasing time intervals and that rat dentin had the highest values of the observed parameter. Comparing the representatives of the Cerabone group, the highest bone volume values were found in the Cerabone with magnesium group. The same trend was observed in the mentioned groups for the thickness and number of bone trabeculae. TNF-α showed the highest tissue expression in the Cerabone group with magnesium, while the expression was the same for OSX, BMP-2/-4, BMP-7, TGF-β, SMAD-1/-5/-8, SMAD-2/3, HO-1, while COX-2 was the largest in the Rat dentin group. Expression of VEGF was the highest in the group of dentin. The ratio of M1/M1MNGC to M2/M2MNGC macrophages significantly increased in the late stages of healing in the Dentin and Rat dentin groups, while in the Cerabone and Cerabome with magnesium groups this increase was determined on the 15th day of healing. Gene expression of SOST showed a proportional relationship with bone volume in the Dentin and Rat dentin groups, while the same, but also the serum concentration of VEGF and RANK was inversely proportional to bone volume in the Dentin group. The serum concentration of HO-1 was inversely proportional to the bone volume in the Cerabone with autologous bone, Dentin and Control groups, while the gene expression of RUNX-2 was directly proportional to the bone volume in the Cerabone and Dentin groups Conclusions: The most primal biomaterial in the healing of the bone defect of the rat calvaria is Rat dentin. The new biomaterial of animal origin Cerabon with magnesium shows better osteoconductive properties compared to the commercial animal biomaterial Cerabon and its mixture with autologous bone.