Periodontal disease is a chronic inflammatory, multifactorial condition, that, in the absence of an early and adequate treatment, may lead to a progressive damaging of the alveolar tissues that support the teeth (periodontal ligament, cement and alveolar bone) followed by teeth mobility and, subsequently, their loss. Periodontal disease is one of the most common inflammatory disease affecting adult individuals all over the world, being considered a real worldwide pandemic. This disease may influence the progression of certain systemic diseases: diabetes mellitus, cardiovascular diseases, ischemic cardiomyopathy, myocardial infarction, stroke, neurodegenerative diseases, chronic kidney diseases, cancer, etc. The association between smoking and periodontal disease was described in numerous clinical and epidemiological studies, suggesting that products derived from tobacco burning may change the clinical aspects and the disease progression. The present study analyzed microscopically and immunohistochemically 58 periodontal fragments, from 50 patients, chronic smokers, clinically diagnosed with severe periodontitis. There were highlighted major changes in the gingival epithelium (epithelium thickening, acanthosis, intraepithelial edema, infiltrates of neutrophils or lymphocytes, epithelial necrosis), in the periodontal conjunctive tissue (more or less intense inflammatory infiltrates, microhemorrhages, vascular congestion, intense immunohistochemical expression for some matrix metalloproteinases). The periodontal changes may be the expression of both toxic factors present in tobacco smoke and due to the changes caused by tobacco in the microbial flora of the oral cavity.