Abstract: In reference to the original drug diclofenac etalhyaluronate sodium (DF-HA), a graft copolymer was synthesized by covalent bonding. The structure of DF-HA was characterized by ¹H NMR, UV-Vis spectrophotometry and FT-IR. The results showed that DF-HA was successfully synthesized, and the grafting rate was determined to be approximately 17% by ¹H NMR and UV-Vis spectrophotometry. The in vitro release of DF-HA graft copolymer was studied by HPLC, and its release of diclofenac (DF) in phosphate buffered saline (PBS, pH 7.4) was investigated. The drug release rate of free DF was 83.6% after 6 h, and that of DF-HA was 4.8% within 1 d and 17.7% within 21 d, which were basically consistent with the release behavior of the reference listed drug. DF-HA could significantly achieve the sustained release of DF, and high molecular weight hyaluronic acid itself had the effect of treating osteoarthritis. With both advantages, DF-HA could have good application value.