The present study aimed to evaluate the modulatoy effects of caffeic acid on the histological, histochemical, immuno-histochemical and ultrastructural changes in the liver of diethylnitrosamine-treated rats. This study was assessed in male albino rats (120-150 g). The rats were divided into four groups. The 1st group was regarded as control. The 2nd group was treated with caffeic acid (CAPE) (10 mg/kg body weight). The 3rd group was injected with diethylnitrosamine (DEN, 10 mg/kg body weight, 5 times/week). The 4th group was injected with DEN and then received a daily dose of (CAPE, 10 mg/kg body weight). The animals were sacrificed after six weeks of treatment. The present histological study revealed that DEN caused marked changes in the liver including mononuclear cell infiltration, vacuolar degeneration, fatty change, blood vessel congestion, in addition to deposition of collagen fibres in the hepatic tissue. Moreover, ultrastructural observations in the liver including vacuolation, fibrosis, break down of endoplasmic reticulum, damage of mitochondria and nuclear changes were studied. The histochemical results revealed that DEN displayed depletion of glycogen, proteins and DNA in the liver tissues. Immuno-histochemical findings revealed increased proliferating cell nuclear antigen (PCNA) cells and strong ions reaction in the liver tissue of DEN-treated group. On the other hand, treatment with caffeic acid led to apparent repair of the injured liver tissues confirming the efficacy of this antioxidant in ameliorating the damaging effect of DEN. This protection may be due to the antioxidant properties and scavenging abilities of caffeic acid against active free radicals.