Aim. To study the immunohistochemical expression of matrix metalloproteinase and tissue inhibitors of matrix metalloproteinase-2 in different histological grades of tobacco associated epithelial dysplasia and correlate the association between these proteases. Potentially malignant oral disorders (PMODs) progressing to oral cancer are related to the severity of epithelial dysplasia.Methods. A retrospective immunohistochemical study was carried out on 30 clinically and histologically proven cases of leukoplakia with dysplasia and 10 cases of normal buccal mucosa using anti-MMP-2 and anti-TIMP-2 monoclonal antibodies.Results. Mann WhitneyUtest, for comparing the expression of both MMP-2 and TIMP-2 in normal mucosa with dysplasia, was highly significant (P<0.001). Kruskal-Wallis test to compare the median score of MMP-2 and TIMP-2 in different grades of dysplasia showed statistical significance (P<0.001), and a Spearman’s correlation between MMP-2 and TIMP-2 through different grades of dysplasia and cells observed showed positive correlation.Conclusion. Concomitant increase in the expression of both MMP-2 and TIMP-2 suggested that the activation of MMP-2 is dependent on TIMP-2 acting as a cofactor. Changes in TIMP-2 levels are considered important because they directly affect the level of MMP-2 activity.