The aim of this study was to investigate matrix metalloproteinase (MMP) expression during the immune response to pulmonary Cryptococcus neoformans (Cne) infection. The immune response generated in C.B-17 and C57BL/6 mice to pulmonary Cne infection has previously been characterized as type 1 and type 2, respectively, differing in the cytokines produced and leukocytes recruited during infection, influencing the extent of Cne clearance from the lung. The focus of this study was to examine changes in expression of MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 in the lungs of Cne-infected mice during the two types (type 1 vs. type 2) of responses. C.B-17 mice that formed well-defined granulomas had elevated levels of pulmonary MMP-2 mRNA early during infection. C57BL/6 mice that had poorly defined cellular aggregates did not express detectable levels of pulmonary MMP-2 mRNA until later in the infection. Specific expression of MMP/TIMP was correlated with the type of immune response present, resolution of Cne infection and the resulting lung pathology.