Abstract: Objective To analyze the differential proteomic profiles of the plasma in patients with chronic hepatitis B presenting with damp-heat retention syndrome and liver stagnation-spleen deficiency syndrome. Methods Two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify the differentially expressed proteins in the plasma of patients with chronic hepatitis B. Results The numbers of plasma proteins detected in healthy volunteers, patients with damp-heat retention syndrome, and patients with liver stagnation-spleen deficiency syndrome were 278 ± 16, 320 ± 14 and 343 ± 19, respectively. Seven differential protein spots were successfully identified by mass spectrum, and were classified into immunological proteins, inflammatory proteins, and lipid metabolism-related proteins. Conclusion In patients with chronic hepatitis B, the multiple differential proteins between damp-heat retention syndrome and liver stagnation-spleen deficiency syndrome suggests the diverse molecular basis of traditional Chinese medicine syndromes, and they might be the molecular tags for different syndromes of the same disease.