BACKGROUND:: When the cells were stimulated by various cytokines and the environment, c-JUN terminal kinase signaling pathway can regulate cell growth, differentiation, apoptosis, cancer, inflammation and the immune response by activating different receptors. OBJECTIVE:: To investigate the inhibition of berberine (BBR) on COX-2 mRNA and protein expression via c-JUN terminal kinase signaling cascade pathways in human peripheral blood mononuclear cells. METHODS:: Mononuclear cells were isolated and cultured from peripheral vein blood and divided into five groups treated with blank control, lipopolysaccharide (LPS), LPS+BBR 25 μmol/L, LPS+BBR 50 μmol/L, LPS+BBR 100 μmol/L respectively. Monocytes were extracted at 30 minutes, 6 hours, 12 hours and 24 hours following culture. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized to examine COX-2 mRNA levels. Western blot analysis was used to measure c-JUN terminal kinase and COX-2 protein levels. Simultaneously, selectivity c-JUN terminal kinase inhibitor was added to examine COX-2 mRNA and protein expression. RESULTS AND CONCLUSION:: Compared with the blank control group, COX-2 mRNA and protein expression of LPS group significantly increased (P < 0.01). COX-2 mRNA and protein expression significantly decreased after different concentrations of BBR treatment (P < 0.05). With the increased concentration of BBR, the COX-2 expression decreased progressively. After the administration of 12 hours, the COX-2 mRNA and protein expression reduced more prominently than that of the other time points. However, there was no significant change in the level of c-JUN terminal kinase activity (P > 0.05). Following the treatment of LPS+ BBR at the concentration of 100 μmol/L, c-JUN terminal kinase activity levels were significant (P < 0.05). COX-2 mRNA and protein expressions were inhibited significantly following incubated with c-JUN terminal kinase inhibitor (P < 0.05). Results have confirmed that BBR inhibits COX-2 mRNA and protein expression in human peripheral blood mononuclear cells in a dose-dependent manner. c-JUN terminal kinase active protein expression can be significantly inhibited by BBR at a high dose. BBR inhibits COX-2 mRNA and protein expression in human peripheral blood mononuclear cells perhaps via c-JUN terminal kinase pathway.