Objective To investigate target moleculars and signal pathways involved in chronic sinusitis, nasal polyps. Methods Proteins were extracted from chronic sinusitis, nasal polyps and normal nasal mucosa tissue, and were separated by the immobilized pH4-7gradient two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. The peptide mass fingerprint and sequence tag of differentially expressed-proteins were gotten with PDQuest analysis software, MALDI-TOF-MS and ESI-Q-TOF-MS, and Mascot searching in NCBInr and SWISS-PROT databases. Ssignal pathways which these proteins involved in were analyzed by linking KEGG web, searching KEGG PATHWAY databases, and P value of ultra geometric distribution was counted. Results The protein spots separated and visualized in chronic sinusitis, nasal polyps and normal nasal mucosa tissue gel were 1112 +/- 10, 1020 +/- 40 and 1008 +/- 25 respectively. And the match rates were (95 +/- 1) %, (93 +/- 2) % and (90 +/- 3) % respectively. Compared to normal nasal mucosa tissue, thirty protein spots were differentially expressed among those nasal mucosa tissue gels. 13 spots of them could be labeled and involved in 18 signal pathways which including the fatty acid metabolism pathway, PPAR pathway and cell communication pathway. A large number of mark proteins in disease could be more rapidly taken with uniting proteomics technology and bioinformatics technology. Conclusion These signal pathways may be an important mark of molecule typing of chronic sinusitis, nasal polyps.