Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-γ) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 μmol/kg/day, respectively). (5: Sham group: CAPE (10 μmol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-γ level, increase the animals′ body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis.