Aim To observe the impact of oxidized low density lipoprotein(ox-LDL) on the expression of interleukin-6(IL-6) in rat vascular smooth muscle cells(VSMC) and investigate the role of toll like receptor 4(TLR4)/mitogen-activated protein kinase(MAPK)signaling pathway in this process.Methods VSMC were incubated with different concentrations of ox-LDL,the expressions of TLR4 mRNA and IL-6 mRNA were determined by reverse transcription-polymerase chain reaction(RT-PCR).The level of IL-6 in supernatant medium was detected by enzyme linked immuno sorbent assay(ELISA).Involvement of TLR4 for the phosphorylations of ERK1/2,P38 and JNK was shown using specific blocking anti-TLR4 antibody and the protein expressions were determined by Western blot.To confirm the involvement of TLR4/MAPK signaling pathway in the expression of IL-6 induced by ox-LDL,VSMC were pretreated with PD98059,SB203580,SP600125 and anti-TLR4 antibody respectively.Results After incubated with different concentrations of ox-LDL,the expressions of TLR4mRNA and IL-6 of VSMC were significantly up-regulated in a concentration-dependent manner(P<0.05).The phosphorylations of ERK1/2,P38 and JNK induced by ox-LDL were dramatically suppressed in the presence of anti-TLR4 antibody(P<0.01).The expression of IL-6 was attenuated by pretreated with PD98059,SB203580 and anti-TLR4 antibody prior to ox-LDL exposure(P<0.01),while SP600125 did not have the effect.Conclusion Our results demonstrate that ox-LDL can up-regulate the expression of IL-6 and the activation of TLR4 signaling in VSMC induced by ox-LDL may partly mediate the up-regulation of IL-6 via activation of ERK1/2 and P38.