Cystic lesions are considered to be one of the most common pathologies of the maxillofacial region, and matrix metalloproteinases (MMPs) may represent potential etiological factors. The aim of the present study was to elucidate the role of MMP-2 and MMP-9, and their endogenous tissue inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, respectively, in the pathogenesis of maxillofacial cystic lesions. A total of 25 patients diagnosed with radicular cysts (RCs; n=20), dentigerous cysts (n=3) and retention cysts (RtCs; n=7) were enrolled in the present study. Gelatin zymography was performed to assess the gelatinolytic activity of MMP-2 and MMP-9, and commercial ELISA kits were used to determine TIMP-1 and TIMP-2 concentrations. Gelatin zymography revealed the presence of both MMP-2 and MMP-9 in all types of samples analyzed. An increase in MMP-9 activity, TIMP-1 concentration and MMP-9/TIMP-1 ratio was observed in the fluid obtained from RCs compared with that obtained from RtCs. In conclusion, MMP-9 may be involved in the pathogenesis of RCs, whereas the activity of MMP-2 in the wall of RtCs was low, and this gelatinase did not appear to significantly affect the development of this type of lesion.