Aim To investigate the effect of hyaluronic acid (HA) on the expression of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in human aortic vascular smooth muscle cell (HA-VSMC) induced by free fatty acid (FFA). Methods HA-VSMCs were cultured and dealt with different concentrations (0,0, 0,0 μmol/L) of FFA and FFA plus high molecular weight HA (HMW-HA) or low molecular weight HA (LMW-HA) for 4,8 hours. The effects of FFA and FFA plus HA on the survival rate of HA-VSMCs were detected by methyl thiazolyl tetrazolium (MTT) method. Cell proliferation activity was detected by EdU staining. The contents of IL-6, IL-8 and TNF-α in culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative PCR and Western blot were used to detect the expression levels of IL-6, IL-8 and TNF-α mRNA and protein. Results(1)FFA showed a concentration-dependent induction to HA-VSMC proliferation in the 400 μmol/L. (2)HMW-HA and LMW-HA both inhibited the proliferation of HA-VSMC induced by FFA, and the inhibitory effect of HMW-HA was stronger than that of LMW-HA. (3)FFA significantly promoted the secretions of HA-VSMC IL-6, IL-8 and TNF-α in a apparent time- and concentration-dependent manner; HA could inhibit the above effect. (4)Real-time fluorescence quantitative PCR and Western blot results showed that the expression levels of IL-6, IL-8, TNF-α mRNA and protein in FFA＋HMW-HA group and FFA＋LMW-HA group were lower than those in FFA group (all P＜0.01), where the FFA＋HMW-HA group was lower than the FFA＋LMW-HA group (P＜0.01). Conclusions (1)FFA can induce the increases of IL-6, IL-8 and TNF-α mRNA and protein expressions in HA-VSMCs. (2)HA can inhibit the expressions of IL-6, IL-8 and TNF-α induced by FFA, and the inhibitory effect of HMW-HA is stronger than that of LMW-HA.