Objective To discuss influence and curative effect observation of sodium hyaluronate on serum matrix metalloproteinase-9,12 and 13 (MMP-9, 12 and 13) levels of patients with knee osteoarthritis (OA). Methods Selected 70 cases of patients with knee OA, and divided into observation group (n=35 cases) and control group (n=35 cases) in accordance at random. The patients in two groups were given oral 75 mg diclofenac sodium enteric capsules , once a day for 5 weeks. The patients in observation group were additionally given 2 mL sodium hyaluronate , injected into in-tra-articular, once a week, for 5 weeks. Excepted for sodium hyaluronate injection fluid, the patients in control group were given the same medical treatment as that in observation group. The changes of serum MMP-9 , 12 and 13 levels between the two groups before and after medical treatment were observed , and the clinical curative effect and untoward effect was compared as well. Results After 5 weeks’ treatment, the serum MMP-9, 12 and 13 levels of patients in two groups were declined more significantly than before with different degrees (P<0.05 or P<0.01), and the declining rate of patients in observation group was much higher than that in control group (P<0.05). The clinical good and excellent rate with in observation group(85.71%) was much higher than that in control group (62.86%)(χ2=4.79,P<0.05). 9 and 11 cases of untoward effect were appeared between control group and observation group respectively with light symp-tom, and after comparing the occurrence rates of untoward effect of patients in two groups, with no statistical differ-ences (χ2=0.28,P>0.05). Conclusion Sodium hyaluronate has favorable curative effect on patients with knee OA, whose mechanism of action has close effect on reducing serum MMP-9 ,12 and 13 levels.