The most common periodontal disease is chronic periodontitis, the inflammatory destructive condition of microbial etiology. Drugs like cyclosporine-A, nifedipine and phenytoin induce overgrowth of the gingiva in 60% of the patients ingesting the drug in the presence of inflammation. During inflammation cytokines derived from inflammatory cells could induce angiotensin II (Ang II) and endothelin-1 (ET-1). Ang II is the effector peptide of renin angiotensin system plays a major role in regulation of collagen synthesis and growth modulating effects on fibroblasts. Endothelin-1 is a powerful vasoconstrictor with mitogenic activity on vascular smooth muscle and fibroblasts. Studies have shown that Ang II and ET-1 were increased in cardiac, renal and pulmonary fibrosis. Since inflammation is prerequisite for drug induced gingival overgrowth (DIGO), mast cells play a major role in the conversion of Ang II and ET-1. This study designed to assess the expression of Ang II, ET-1 and its receptors, mast cell chymase; tryptase and transcription factor c-jun in CsA induced gingival fibroblasts and drug induced gingival overgrowth tissues obtained from kidney transplanted patients.