Aim To investigate the association between high density lipoprotein (HDL) subclasses and IL-6 concentration in patients with metabolic syndrome (MS). Methods The MS subjects (n=135) and healthy controls (n=77) were selected. The levels of IL-6 were determined by enzyme-linked immunosorbent assay (ELISA) kits. According to the levels of plasma IL-6, the MS subjects were divided into three groups:low IL-6 group (IL-6≤66.76 ng/L), middle IL-6 group (66.76 ng/L3b, HDL_3c, plasma total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC), LDLC/HDLC and ApoB₁₀₀/ApoAI were significantly increased in MS subjects (P<0.05 or P<0.01), while HDL_2a, HDL_2b, preβ2-HDL, apolipoprotein AI (ApoAI) and high density lipoprotein cholesterol (HDLC) were significantly decreased in MS subjects (P<0.05 or P<0.01). Compared with the control group of the same sex, the relative content of HDL subclass of male or female in MS group was significantly different (P<0.05 or P<0.01). Compared with the same group of males, the level of lipids, apolipoproteins in control group and MS group were no statistical significance (P>0.05). The correlation analysis showed that IL-6 was positively correlated with the level of preβ1-HDL and HDL_3b and negatively correlated with the level of HDL_2b. Conclusion The plasma IL-6 levels were increased in MS patients, and the particle size of HDL showed a shift toward smaller size. The increasing of IL-6 may be related to HDL subclasses distribution abnormality and dyslipidemia.