Matrix metalloproteinase‐2 (MMP‐2) may play roles at intracellular and extracellular sites of the heart in ischaemia/reperfusion injury. Caveolins (Cav‐1, ‐2 and ‐3) are lipid raft proteins which play roles in cell sig‐nalling. This study examined, using immunohistochemistry and two photon confocal microscopy, if MMP‐2 and caveolins co‐localize at the plasma membrane of cardiac cells: cardiomyocytes (CM), fibroblasts (FB) and capillary endothelial cells (CEC) in the left ventricle (LV) of the Cav‐1^+/+ and Cav‐1^−/− mouse heart. In Cav‐1^+/+ mouse LV MMP‐2 and Cav‐1 co‐localized at CM plasma membranes, and at multiple locations in FB and CEC. MMP‐2 co‐localized with Cav‐2 only at CEC. MMP‐2 co‐localized with Cav‐3 at CM plasma membranes and Z‐lines, and partially at FB and CEC. In Cav‐1^−/− LV Cav‐1 and MMP‐2 were absent or reduced everywhere. Cav‐2 appeared at CEC despite the absence of Cav‐1. Cav‐3 appeared at CM plasma membranes and Z‐lines, FB and CEC. Also, FAK in FB and c‐Kit in interstitial Cajal‐like cells (ICLC) were completely absent. By transmission electron microscopy in Cav‐1^+/+, regular size caveolae (Cav) were at CEC, irregular size Cav were at CM and a few were at FB. In Cav‐1^−/− there were few Cav at CM and FB and some at CEC. To conclude, MMP‐2 is closely associated with caveolins at FB and CEC as well as at CM. Also, MMP‐2 is closely associated with FAK at FB and c‐Kit at ICLC. Thus, Cav‐1 expression is not necessary for Cav‐2 expression. Cav‐3 or Cav‐3 with Cav‐2 has the capability to make Cav.