The aim of this study was to evaluate the immunomodulatory effect of the staphylococcal vaccine inoculated subcutaneously in 15 patients with chronic periodontitis. Bacteriological investigation of samples collected from the periodontal pocket for aerobic and anaerobic microorganisms was performed by classic bacteriological procedures before and after vaccination. The following immune system parameters were evaluated: C reactive protein (CRP), serum level of C3 complement fraction, IgG, IgA, and IgM by immunodiffusion, PMN granulocytes ROS release after in vitro stimulation with opsonized zymosan (OZ) and Concanavalin A (ConA) by chemiluminescence assay and lymphocytes sets and subsets by flow-cytometry immunophenotyping. The microbiological investigations revealed high frequency of Staphylococcus spp isolation and the presence of the most common anaerobe agents incriminated in human periodontitis like Fusobacterium, Porphyromonas, Peptostreptococcus, Veillonella spp and the reduction of this flora in the periodontal pocket after therapy. The immunological parameters quantification showed the absence of CRP, normal values of C3, IgG, IgA, IgM in the majority of cases. All patients presented normal values of lymphocytes sets and subsets. Significant increase of PMN respiratory burst after ConA stimulation was observed before vaccination which turned to normal values after therapy and a low ROS level both before and after therapy suggesting PMN Fc receptors dysfunction in this group of patients. The data presented in our study suggest an immunomodulatory effect of staphylococcal vaccine therapy in periodontitis and high frequency of Staphylococcus spp recovering from the periodontal pocket of investigated subjects.