Objective To explore the effects of 4-phenylbutyric acid (4-PBA) on idiopathic pulmonary fibrosis (IPF) using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal injection of BLM. A total of 120 mice were randomly allocated into three groups: BLM group, BLM+4-PBA group, and control group. Pathology of lung tissue was analyzed to evaluate the degree of pulmonary fibrosis, and the survival of the mice was noted. The expression levels of the endoplasmic reticulum stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were analyzed in lung tissues from mice. Results BLM induced significant collagen deposition in the lungs of the mice, which was alleviated by 4-PBA. 4-PBA also dramatically improved the pulmonary function and increased the survival rate in the BLM+4-PBA group compared with that in the BLM group. Both the mRNA and protein expression levels of ATF6 and CHOP were significantly reduced in mouse lung tissue after 2 weeks of 4-PBA treatment. Conclusions 4-PBA treatment could alleviate BLM-induced pulmonary fibrosis in mice via the attenuation of endoplasmic reticulum stress.