To investigate the signal pathways involved in cyclooxygenase-2 (COX-2) expression in chronic rhinosinusitis (CRS). The expressions of COX-2, p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK), and nuclear factor kappa B (NF-kappa B) in nasal mucosa were detected by immunohistological stain and polymerase chain reaction (PCR). Their expressions and prostaglandin E2 (PGE(2)) release were determined by PCR, Western blot and enzyme immunoassay (EIA) in human nasal epithelia (HNE) cells after lipopolysaccharide (LPS) induction, and/or small interfering RNA (siRNA) transfection. Positive protein expressions of COX-2, p38MAPK, ERK, NF-kappa B subunits were detected in epithelial and inflammatory cells. Their mRNA levels were significantly higher in CRS than controls (P < 0.05). The expressions varied in time and concentration-dependent manner in LPS-induced HNE cells. COX-2 expression was suppressed by siRNAs of P38MAPK, ERK, and NF-kappa B; however, COX-2-specific siRNA had no blocking effect on them. SiRNAs of P38MAPK or ERK could block NF-kappa B, but NF-kappa B-specific siRNA had no blocking effect on the former. SiRNA of p38MAPK, or ERK did not inhibit each other. Upregulation of COX-2 expression suggested its role as a mediator in CRS. ERK and p38MAPK pathways were involved in signaling COX-2 through NF-kappa B pathway.