Lian Y, et al. - A total of 25,130 individuals without dyslipidemia at baseline were incorporated in order to investigate the impact of metabolic-related markers on dyslipidemia and to evaluate what extent inflammation mediating these correlations. Lipid metabolism, blood pressure, obesity condition, glucose metabolism, renal function, and lifestyle, all these factors had a diverse influence on the development of dyslipidemia, directly and (or) indirectly. Partial least squares path analysis showed that the determination coefficient of the model (R2) was 0.52. Lipid metabolism, obesity condition, and glucose metabolism, all these factors had both a direct and indirect impact on dyslipidemia via inflammatory factors. The most significant risk factor in the prediction of dyslipidemia was the lipid metabolism factor, followed by the obesity condition factor and glucose metabolism factor. In conclusion, for dyslipidemia, metabolic-related markers were robust risk factors. Inflammatory factors have an important mediating influence on these associations. These findings recommended that comprehensive intervention approaches about metabolic biomarkers and inflammatory factors should be taken into account in the prevention and treatment of dyslipidemia.