Background:Actinobacillus actinomycetemcomitans’ lipopolysaccharide (LPS) has a high virulence factor. It interacts with serum protein through receptors on the epithelial cell surface, thereby increasing both interleukin (IL)-1β, and IL-6 which results in damage to periodontal tissue.Aim:The aim of the study was to identify and evaluate the effect of LPS derived from local isolates (A. actinomycetemcomitans) on the destruction of alveolar bone by means of several biomarkers, including; the number of osteoblasts and osteoclasts, the expression of IL-6, matrix metallopeptidase 1 (MMP-1), and receptor activator of nuclear factor kappa-Β ligand (RANKL).Materials and Methods:The isolation of LPS from A. actinomycetemcomitans was calculated using phenol, while purification was performed using Sephadex C-18 column chromatography. 40 Wistar rats were divided into four groups of 10. Each treatment was divided into two groups which were 0.9% NaCl and LPS induced for 7 and 14 days, respectively. Gingival and alveolar bones were further introduced into the induction area, followed by the measuring of osteoblast and osteoclast with hematoxylin-eosin staining, IL-6, MMP-1 and RANKL expression with immunohistochemical.Results:Reduced numbers of osteoblasts at the 7th and 14th day of treatment were detected, while those of osteoclasts increased. There was an increased expression of IL-6, MMP-1, and RANKL in the 7th and 14th-day treatment group. Treatment of LPS from A. actinomycetemcomitans over 7 and 14 days resulted in damage to periodontal tissue and alveolar bone in Wistar rats.Conclusion:LPS of A. actinomycetemcomitans administration for 7 and 14 days causes periodontal and alveolar tissue destruction in Wistar rats.