Cold exposure can induce a form of environmental stress. Cold stress (CS) alters homeostasis, results in the creation of reactive oxygen species and leads to alterations in the antioxidant defense system. The caffeic acid phenethyl ester (CAPE), an active component of propolis, has an antioxidant capacity. We investigated the effect of CS on oxidative stress and antioxidant defense system and the possible protective effect of CAPE in rat liver tissue. Twenty-four female Wistar Albino rats were divided into four groups: Control, CAPE-treated, CS, and CAPE-treated CS (CS + CAPE) group. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and total glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, histological changes in liver tissue were examined by light microscopy. SOD, CAT and GSH-Px activities and total GSH level were significantly declined in the CS group. In the CS + CAPE group, the activities of these three enzymes and GSH level significantly raised with regard to the CS group. MDA levels increased in the CS group and decreased in the CS + CAPE group. The tissues of the CS group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the CS + CAPE group, the histopathological evidence of hepatic damage was markedly reduced. Histological parameters were consistent with biochemical parameters. In this study, CS increased oxidative stress in liver tissue. CAPE regulated antioxidant enzymes, inhibited lipid peroxidation and reduced hepatic damage.