Aim To detect the effect of neuropeptide Y (NPY) on the expression of low density lipoprotein receptors (LDLR) in human vascular smooth muscle cells (hVSMC). Methods The cultured hVSMC in vitro were divided into the control groups and the different concentration NPY groups (the concentrations of NPY were 10 8 mol/L, 10 7 mol/L, 10 6 mol/L and 10 5 mol/L). All groups were cultured for 6 h, 12 h, 24 h and 48 h respectively, then, were stained by the immunofluorescent histochemical staining and quantitatively assayed the effect of NPY on the expression of LDLR in hVSMC under laser scanning confocal microscope. Results The averaged fluorescent values of the LDLR expression in hVSMC of control groups were 2 428 to 2 527, and there were no significant differences among the different culture times (p>0.05), while there were significant differences between the averaged fluorescent values in NPY groups and those in control groups (p<0.05 or p<0.01). The averaged fluorescent values were 1 798 to 2 408 in 10 8 mol/L NPY groups, 1 783 to 2 332 in 10 7 mol/L NPY groups, 1 722 to 2 281 in 10 6 mol/L NPY groups and 1 590 to 2 010 in 10 5 mol/L NPY groups during the different culture times, decreasing averagely by 15.59%, 19.78%, 21.91% and 26.83% compared with control groups respectively, and there were significant differences among most of the different concentration NPY groups (p<0.01). NPY donwregulated the expression of LDLR in hVSMC with dose dependent and time dependent manner. Conclusion Neuropeptide Y could downregulate the expression of LDLR in hVSMC, then it probably resulted in blocking the LDLR mediated pathway, consequently LDL could accumulated in the vascular wall. This might be the important mechanism that neurofluid factor participated in the occurrence of atherosclerosis.