Objective Assessment of the comprehensive relationship among apolipoprotein CIII(apoCⅢ) levels, inflammation, and metabolic disorders is rare. Methods A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCⅢ in the association of inflammation with metabolic syndrome(MetS). Results Patients with MetS showed higher levels of apoCⅢ [95.1(73.1-131.4) vs. 81.7(58.6-112.4) μg/mL, P < 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7(0.8-3.4) vs. 1.1(0.5-2.2) mg/L; white blood cell count,(6.48 ± 1.68) vs.(6.11 ± 1.67) × 10~9/L]. The levels of apoCⅢ and inflammatory markers increased with the number of metabolic risk components(all P < 0.001). Furthermore, apoCⅢ levels were associated with virtually all individual MetS risk factors and inflammatory markers(all P < 0.05). Importantly, the prevalence of MetS in each metabolic disorder rose as apoCⅢ levels increased(all P < 0.05). Mediation analysis showed that apoCⅢ partially mediated the effect of inflammation on MetS independently from triglycerides. Conclusion Plasma apoCⅢ levels were significantly associated with the development and severity of MetS, and a role of apoCⅢ in the effect of inflammation on the development of MetS was identified. Objective Assessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare. Methods A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoC III in the association of inflammation with metabolic syndrome (MetS). Results Patients with MetS showed higher levels of apoC III [95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg / mL , P <0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7 (0.8-3.4) vs. 1.1 (0.5-2.2) mg / L; white blood cell count, (6.48 ± 1.68) vs. (6.11 ± 1.67 ) X 10-9 / L]. The levels of apoCIII and inflammatory markers increased with the number of metabolic risk components (all P <0.001). Furthermore, apoC III levels were associated with virtually all individual MetS risk factors and inflammatory markers (all P <0.05). Importantly, the pre valence of MetS in each metabolic disorder rose as apoCIII levels increased (all P <0.05). Mediation analysis showed that apoC III partially mediated the effect of inflammation on MetS independently from triglycerides. Conclusion Plasma apoC III levels were significantly associated with the development and severity of MetS , and a role of apoCIII in the effect of inflammation on the development of MetS was identified.