This study was to investigate the expression and significance of ER stress related protein GRP78 and CXCL12 in idiopathic pulmonary fibrosis. 55 biopsy or surgical specimens from idiopathic pulmonary fibrosis patients were collected in Jingzhou Central Hospital from 2009 to 2017, 10 cases of normal lung tissue as control. Western blotting was used to detect GRP78 and CXCL12 protein expression, and RTPCR to detect GRP78 and CXCL12 expression in mRNA level. Results showed that compared with the control group, the expression of GRP78 and CXCL12 proteins in the alveolar epithelium of lung fibrosis patients were up-regulated, also the expressions of GRP78 and CXCL12 in mRNA level were upregulated. And regressive analysis revealed that there was a positive relationship between GRP78 and CXCL12 in protein and mRNA level statistically. This suggested that GRP78/CXCL12 axis may be involved in the pathogenesis and development of idiopathic pulmonary fibrosis.