Aim To investigate the correlation between erythropoietin-producing hepatocellular receptor A2 (EphA2), progranulin (PGRN), and endothelial inflammatory and adhesion factors in patients with coronary artery disease (CAD). Methods From January to December 0,3 CAD patients who were admitted to the Department of Cardiology of Zhongshan Hospital Affiliated to Fudan University for coronary angiography were selected. 5 mL of elbow vein blood was collected on an empty stomach the next morning after admission. Serum EphA2 and PGRN levels were determined by ELISA, and serum tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and interferon-γ (IFN-γ) levels were determined by Premixed Luminex. Results The levels of serum EphA2, N-terminal pro-brain natriuretic peptide (NT proBNP), cardiac troponin T (cTnT), high sensitivity C-reactive protein (hs-CRP), creatine kinase isoenzyme-MB (CK-MB) myocardial injury markers in patients with acute coronary syndrome (ACS) were 6.3 times, 15 times, 161 times, 13 times, 2.5 times higher than those in patients with chronic coronary syndrome (CCS) (P＜0.001), and serum TNF-α, IL-6 and VCAM-1 were 37.9%, 500.0% and 196.6% higher than those in CCS patients (P＜0.01), and serum PGRN levels were not significantly higher than those in CCS patients (P＝0.051). The area under curve (AUC) of serum EphA2, PGRN, IL-6, and VCAM-1 in predicting ACS were 0.2,0.6,0.926 and 0.861 respectively. Serum EphA2, VCAM-1, IL-6, TNF-α and MCP-1 was positively correlated with Gensini scores (r＝0.533, P＜0.001; r＝0.549, P＜0.001; r＝0.621, P＜0.001; r＝0.263, P＝0.027; r＝0.264, P＝0.026). Serum EphA2 was positively correlated with IL-6 and VCAM-1 respectively (r＝0.565, P＜0.001; r＝0.474, P＜0.001). There was no correlation between PGRN and inflammatory factors and adhesion factors (P＞0.05). Serum PGRN and EphA2 were positively correlated with myocardial injury markers (P＜0.05). Conclusions This study supports that EphA2 is involved in the process of endothelial inflammation in the acute stage of plaque injury from a clinical perspective, and suggests that EphA2 and PGRN may be potential targets to intervene in endothelial inflammation and predict the progression of atherosclerotic lesions.