Matrix proteinases are known to play an important role in the cell migration during cancer invasion, in organ development, and in tissue damage during inflammatory process. Among the matrix proteinases, matrix metalloproteinases (MMP) are the most powerful proteinases. Changes at the extracellular matrix components play an essential role in acute rejection after orthotopic liver transplantation (OLT). This prospective clinical study investigated the alterations in the expression of MMP-2 (72-kd gelatinase type IV collagenase [gelatinase A]) and MMP-9 (92-kd gelatinase type IV collagenase [gelatinase B]) in patients with acute cellular rejection (ACR) compared with the biopsies of cirrhotic livers (CL) of patients who underwent OLT, and with healthy livers (HL) of the donors. Although MMP-2 expression was not present in the hepatocytes of the HL, it was in the endothelium; it was moderate in CL and severe in the livers suffering from ACR. MMP-9 expression, on the other hand, is found to be present only in the inflammatory cells, with an increasing intensity in HL, CL, and in livers suffering from ACR. The results suggest that MMP-2 and MMP-9, beside their roles in liver injury with tissue remodeling and fibrosis as mentioned in the previous studies, can be a marker of acute rejection.