Background- Pyogenic granuloma is a common reactive oral lesion characterized by rapid vascular proliferation and tissue remodeling. Matrix metalloproteinase-2 (MMP-2) and its regulators, TIMP-2 and RECK, are key modulators of extracellular matrix turnover and angiogenesis, but their roles in pyogenic granuloma remain unclear. Aim- This study aimed to assess the expression and possible role of MMP-2, TIMP-2 and RECK in the biologic behaviour of Pyogenic granuloma. Methods- This was a laboratory based immunohistochemical study of pyogenic granuloma cases seen at the Department of Oral Pathology/Oral Medicine, UCH Ibadan, Nigeria between January 2000 and December 2011. 50 cases of pyogenic granuloma were sectioned and stained with commercial antibodies for MMP-2, TIMP-2 and RECK. Immunohistochemical staining of cells in individual cases was assessed at X100 magnification. Immunohistochemical assessment of MMP2, TIMP2 and RECK were expressed in proportions/percentages. Mean scores for MMP-2, TIMP-2 and RECK as well as MMP-2: TIMP-2 and MMP-2: RECK in all the cases of pyogenic granuloma were compared using the Independent Sample T test. Results- All of the cases expressed MMP2 and 88% of cases expressed TIMP-2 while RECK is positive in 80%. The mean MMP2: RECK ratio in pyogenic granuloma is 2:1. TIMP -2 is significantly higher in males than females (p = 0.005) while mean MMP2:TIMP2 is significantly higher in females than males (p = 0.000). Pearson correlation and regression analyses were performed to explore the relationships between MMP-2 and its inhibitors, TIMP-2 and RECK, in pyogenic granuloma. A weak negative correlation was observed between MMP-2 and TIMP-2 expression (r = −0.093), which was not statistically significant (p = 0.521). Similarly, simple linear regression analysis showed that MMP-2 expression was not a significant predictor of RECK expression (β = 0.02, p = 0.882), with the model explaining virtually none of the variance (R² = 0.00). Conclusion- MMP-2 is expressed in all pyogenic granuloma cases and exceeds the levels of its inhibitors, TIMP-2 and RECK, consistent with its role in driving angiogenesis. Its expression appears largely independent of TIMP-2 and RECK, suggesting additional regulatory factors influence MMP-2 activity in these lesions.