Objective: To investigate the expression level of alpha-2-macroglobulin in osteoarthritis (OA) cartilage and its role in OA chondrocytes. Methods: Samples of tibia plateau were collected from 24 patients undergone total knee arthroplasty (TKA). The cartilage surface was divided into 2 areas: relative normal area and absolute osteoarthritis area. The primary OA chondrocytes were cultured and divided into three groups: normal culture group (control group), IL-1b stimulation group, IL-1b stimulation and A2M treatment group (A2M group), 24 hours later, mRNA levels of chondrocytes were detected by qPCR, and 48 hours later, the expression of matrix metalloproteinase-13 (MMP-13) was tested by Western blot. The concentration of MMP-13 in supernatant was detected by ELISA. T testand one-way ANOVA were used for statistical analysis. Results: A2M mRNA level in absolute osteoarthritis area of tibia plateau was significantly lower than that in relative normal area (P<0.05). In chondrocytes culture experiment, the level of anabolism in A2M treatment group was significantly higher than that in IL-1b stimulation group (P<0.05), while the level of catabolism was significantly lower than that in IL-1b stimulation group (P<0.05). Western blot and ELISA showed that the level of MMP-13 decreased significantly after A2M treatment. Conclusion: A2M could decrease catabolic metabolism effectively in the chondrocyte culture, may be a new strategy for OA treatment in the future, and next we will test the hypothesis in vivo.