Hepatocyte growth factor (HGF) plays a critical role in transplant rejection. Herein we addressed whether HGF expression could be used for accurate and early diagnosis of acute and chronic rejection in cardiac transplantation. We used a heterotopic cardiac transplantation model using nonhuman primates (Macaca fuscata, n = 7). The grafts were harvested on days 1, 7, 22, 28, 40, 41, and 95 for histology and immunohistochemistry. Histopathologically, HGF was expressed in the spindle-shaped cells of the acutely rejecting myocardium. The expression of HGF was enhanced in both thickened intima and media of the coronary arteries. Altered HGF expression is a sensitive indicator for acute and chronic cardiac rejection.