Aim: To histo-morphologically compare the mast cell density, epithelium thickness, mean vessel density in the gingiva before and after giving mast cell stabilizers. Settings and Design: The present cross-sectional study was conducted on 45 patients diagnosed with chronic periodontitis. Gingival biopsies were obtained from 45 patients categorized into 2 groups: group 1 before giving mast cell stabilizers and group 2 after giving mast cell stabilizers. The groups were sub-categorized as smokers and non-smokers. The epithelial thickness, mean vessel density and number of mast cells were assessed using histo-morphometric analysis. Results of this study revealed that the mean mast cell density and mean vessel density decreased after giving mast cell stabilizers in group 2 compared to group 1. There was no significant difference in the epithelium thickness between both the groups. Conclusion: Mast cells play a crucial role in the sustenance and progression of periodontal disease as mean mast cell density was high before giving mast cell stabilizers.