The present research proposes an assessment of the localized inflammatory burden but also at the systemic level by quantitating the pro-inflammatory molecules (IL1-a, IL1-b, IL2, IL12, IFN-g, TNF-a) with endo-periodontal lesions. The study was performed on a group of 146 subjects who, following clinical and radiological examinations, were divided into five groups: healthy endo-periodontal patients, patients with periodontitis, patients with moderate periodontitis, patients with severe periodontitis and patients presenting combined endo-periodontal lesions. IL1-a, IL1-b, IL2, IL12, IFN-g, TNF-a were analysed in crevicular fluid by ELISA and serum by fluorescence flowcytometry. IL1-a and IL1-b showed serum and crevicular fluid values significantly higher than the healthy subjects. Values for IL2, IL12, TNF-a and IFN-g measured in crevicular fluid were higher for groups II, III, IV, and V compared to the group of healthy endo-periodontal subjects. IL2 showed significantly higher serum values for groups III, IV and V than group I. Serum IL12 values were significantly higher than healthy periodontal subjects only for patients with severe periodontitis and endo-periodontal syndrome. Following serum determinations of proinflammatory molecules, patients with endo-periodontal lesions demonstrated significantly higher values even in subjects with severe periodontitis; these data indicate a much higher risk for these patients to develop and maintain systemic maladies, as is the role local inflammation can play over the general inflammatory status of the patient.