Objective To investigate the effects of (NO), endothelin (ET), substance P (SP) and calcitonin gene-related peptide ( CGRP) immunocompetence substances and their relationship to chronic periodontitis. Methods Immunohistochemical aod histochemical staining methods were used to detect the expression of the NO synthase (NOS), ET, SP and CGRP levels in 20 patients with chronic periodontitis and 20 healthy subjects as control. Results Quantitative analysis by Quantimat 970 showed that NOS and ET in periodontitis tissue increased significantly (P < 0.01), particularly the content of ET in comparison with healthy subjects. The intergroup expression of SP and CGRP showed no remarkable changes. Conclusion Our results demonstrate that the level of NOS and ET were significantly increased in periodontitic tissue, which may diminish the blood supply and influence the periodontal tissue causing tissue damage. Our study suggests that immunocompetence substances NO and ET are closely associated with periodontitis and may play an important role in the disease.