Background This study investigated the inhibitory effect of berberine(BBR)on lipopolysaccharide(LPS)induced cyclooxygenase-2(COX-2)expression via the mitogen activated protein kinase(MAPK)signalling cascade pathways in human peripheral blood monocytes(PBMC).Methods PBMC from whole blood were isolated and cultured for uD 10 24 hours after division into 5 groups treated with LPS,LPS+BBR 25 μmol/L,LPS+BBR 50 μmol/L or LPS+BBR 100 μmol/L and untreated.Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase(p38MAPK),Jun N-terminal kinase(JNK)and extracellular regulated kinases 1/2(ERK1/2)signalling pathways.Results COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment fP＜0.05).With the increasing concentration of BBR treatment,the COX-2 expression decreased progressively(P＜0.01).With BBR treatment for 6,12 or 24 hours at three doses,ERK1/2 protein expression was significantly inhibited.For the JNK pathway,only with the treatment of BBR at the concentration of 100 μmol/L was JNK protein expression inhibited compared with the LPS stimulation group(P＜0.01).Irrespective of the BBR concentration,no difference was shown between the BBR group and the LPS group for p38MAPK protein expression.Human monocytes COX-2 mRNA,by RT-PCR,and protein expression,by Western blot analysis,were inhibited when incubated with PD98059,SP6001 25 and SB203580 (P＜0.05).Conclusions Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and,possibly,at a high dosage via the JNK pathway.P38MAPK may have no relationship with the effect of BBR in PBMC.Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.