Abstract: OBJECTIVE To establish the chromatographic fingerprint of Zexie decoction by UPLC. METHODS The fingerprint was determined on ACQUITYUPLC^ÒBEH C₁₈ column(2.1 mm×50 mm, 1.7 μm), with acetonitrile(A)-water(B) as mobile phase for gradient elution at a flow rate of 0.3 mL·min^-1. The temperature of column was 35℃. Full wavelength scanning was employed and alisma B was chosen as the reference peak. The UPLC fingerprints of 15 batches of Zexie decoction were studied and the similarity was analyzed with Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine combined with principal component analysis and discriminant analysis of orthogonal partial least squares(PLS-DA). RESULTS There were 23 common peaks in the UPLC fingerprints of Zexie decoction. Among of them, 15 common peaks were assigned to Alismatis Rhizoma, 8 common peaks belong to Atractylodis macrocephalae Rhizoma. Atractylenolide I, atractylenolide Ⅱ, atractylenolide Ⅲ, alisol A, alisol B, alisol B monoacetate were determined by the relative time of the standard substance and the contents of these compounds were in range of 0.028 7-0.033 1, 0.029 5-0.036 6, 0.012 0-0.019 4, 0.102 2-0.143 9, 0.469 3-0.701 2, 0.425 5-0.730 8 mg·mL^-1 in 15 batches of Zexie decoction. The similarities of batches were 0.979-0.996. In principal component analysis and PLS-DA, 15 batches of samples were divided into 3 groups according to Alismatis Rhizoma that come from different provinces. CONCLUSION The established method is quick, easy, accurate, stable and repeatable, which can basically reflect the overall chemical composition characteristics of Zexie decoction and provide a reference to the exploitation and application of Zexie decoction.