The endogenous microbiome of the oral cavity plays an essential role in the development of periodontal disease. It also has a significant pathogenic effect on the inner-vation of the oral cavity organs. The experimental determination of the effectiveness of various drugs is required for the effective treatment of periodontal disease, and this involves the creation of a model of experimental periodontitis. The objective of this series of studies was to determine the possibility of reproduction of the experimental model of periodontitis and the study of the effects of anticholinergic drugs on the development of an experimental periodontitis model. The reproduction of the experimental model of periodontitis was performed by injecting the gums of rats with solutions of pathogenic factors: lipopolysaccharide, hyaluronidase and trypsin. We aimed to study the effect of anticholinergic drugs (pilocarpine and atropine) on the development of an experimental model of periodontitis after the injection of a hyaluronidase solution (2 mg/ml) into the rats’ gums. The study was performed on white Wistar rats. Elastase activity, malonic dialdehyde content, urease activity (bacterial contamination index), lysozyme activity (an indicator of nonspecific immunity), and catalase activity (an antioxidant enzyme) were determined in the homogenate of the studied tissues. The results of a comparative study of the effect of three pathogenic factors (lipopolysaccharide, hyaluronidase, and trypsin) on the activity of elastase in different tissues of experimental animals (gums, tooth pulp, serum, and gastric mucosa) showed that hyaluronidase has the greatest proinflammatory effect. The action of pilocarpine and atropine was determined with an underline experimental periodontitis model. It was shown that both anticholinergic drugs stimulate the inflammatory process in the periodontium and that anticholinergic drugs enhance the proinflammatory effect of hyaluronidase.