Periodontal disease is the most widespread disease of all chronic inflammatory diseases. The initiation and development of inflammation in the periodontal tissue is influenced by the number and type of microorganisms and by the inflammatory immune host response. Analytical epidemiology and molecular biology studies in the last decade have shown that periodontal inflammation does not only present a risk for tooth loss, but may also play a role in the development of certain systemic diseases. Periodontal disease plays a role in development of some diseases via direct penetration of microorganisms into the bloodstream through an ulcerated inner gingival epithelium and by increasing the levels of some inflammatory mediators and cytokines in the serum. The aim of our study was to determine the levels of inflammatory mediators (C-reactive protein (CRP), fibrinogen, procalcitonin) and inflammatory cytokines (IL-2, sIL-2R, IL-6, IL-8, TNF-α) in the serum of systemically healthy blood donors with periodontal disease. Our hypothesis was that the size of soft periodontal pocket wall in contact with bacteria (infected periodontal wound) influences the level of inflammatory mediators and cytokines in the serum. For the evaluation of infected periodontal 4 wounds, the cervical circumference was measured at the cemento-enamel junction on 515 extracted teeth. The average values of cervical circumferences of individual teeth were multiplied by the average values of six measurements of probing depth for individual teeth in 31 blood donors. The sum of all products for individual teeth presented the size of the infected periodontal wound for each individual. The sum of all products of periodontal pocket measurements, which bled on probing, presented the size of the active infected periodontal wound. Our study included 31 systemically healthy male blood donors aged between 30 and 56 years (average age 43.2 years). Our periodontal examination included pocket depth probing and bleeding on probing. The association between the area of active periodontal wound and the concentrations of inflammatory mediators and cytokines was tested by calculating the Pearson’s correlation coefficient. A P value of less than 0.05 was considered statistically significant. The results for cervical circumferences in the maxilla ranged from 20.58 to 32.67 mm in the male population, and from 19.69 to 30.95 mm in the female population. In the mandible, the cervical circumferences ranged from 17.53 to 32.19 mm in males, and from 16.07 to 30.48 mm in females. The measured sizes of infected periodontal wounds in 31 blood donors ranged from 4.13 to 27.59 cm2 (average size 17.98 cm2). The measured sizes of active infected periodontal wounds ranged from 0.86 to 25.4 cm2 (average size 10.14 cm2). The statistical analysis showed that among all inflammatory mediators and cytokines observed in the serum of blood donors, only IL-2 and sIL-2R showed a positive correlation with the size of infected periodontal wound. The levels of IL-2 and sIL-2R in the serum were statistically significantly higher (p<0.01), with greater size of infected periodontal wound and deep bleeding periodontal wound. The results of our study show a significantly higher level of serum IL-2 and sIL-2R in systemically healthy male blood donors when greater periodontal tissue destruction is present. If a large number of bleeding periodontal pockets (active infected periodontal wound) is additionally present, the levels of IL-2 and sIL-2R in the serum are even higher.