Objective. To investigate the effects of Qi-Fang-Xi-Bi-Granules (QFXBGs) on cartilage morphology and methylation of C/ebp alpha (CCAAT/enhancer binding protein alpha) at the promoter region. Methods. Knee osteoarthritis (KOA) modeling was performed in rats in accordance with Hulth's method, and control group received sham operation. Eight weeks after KOA modeling, the rats in the KOA modeling group were further divided into 6 groups. Each group was given the appropriate drug. After 8 weeks, half of the rats were used forMicro-CT scan, HE staining, ABH/OG staining, immunohistochemistry, and TUNNEL staining of the knee joint tissue, and the other half were used to examine C/ebp alpha promoter methylation. Results. The three dose groups of QFXBGs all showed lower degrees of surface fissures and flaking, thicker cartilage layer, and restored chondrocyte and subchondral bone morphology, compared with the KOA model group. C/ebp alpha-22 promotermethylation levels in the high-and low-dose groups were significantly higher than that in the KOA modeling group (p < 0.05), while C/ebp alpha-2 promoter methylation level in the medium-dose group was significantly higher than that in the KOA modeling group (p < 0.05). Conclusions. QFXBGs may alleviate articular cartilage degeneration through promoting C/ebp alpha-2 or C/ebp alpha-22 methylation at specific promoter sites.