Objective To explore the effect of Huangqibiejia pills in the treatment of knee osteoarthritis (KOA) by observing the changes of articular cartilage, and the expression of related proteins in hypoxia-inducible factor 1α (HIF-1α) signaling pathway. Methods 60 SD rats were randomly divided into the sham group (10 rats) and model group (50 rats). The ovaries of the rats in the sham group were kept, while the rats in the model group were injected with sodium iodoacetate once in the knee joint cavity 8 weeks after ovary resection. Then the rats were divided into KOA-model group, celecoxib group and Huangqibiejia pills high-dose group, medium-dose group and lowdose group, with 10 rats in each group. The rats in each group were given drug intervention for 4 weeks. After the last administration, the serum estradiol（E2）level, tumor necrosis factor-α（TNF-α) and interleukin-1β (IL-1β) contents of the lavage fluid were detected, and the transverse diameter of the knee joint was measured to observe the appearance and pathological changes of cartilage. The protein expression of cartilage in each group was detected by Western blot. Results The contents of IL-1β and TNF-α in the transverse diameter of knee joint and in the irrigation solution in each dose groups of Huangqibiejia pills were significantly lower than those in the KOA-model group (P<0.05). The level of serum E2 in Huangqibiejia pills high-dose group and Huangqibiejia pills medium-dose group was higher than that in KOA-model group (P<0.05). The surface of the knee cartilage in Huangqibiejia pills high-dose group was smoother than that in KOA-model group, and the defects were not obvious. The middle part of the knee cartilage was slightly damaged and there was vascular hyperplasia in the Huangqibiejia pills medium-dose group. Under microscope, the knee cartilage surface of rats in Huangqibiejia pills high-dose group and Huangqibiejia pills medium-dose group was smooth, the chondrocytes were arranged neatly, the cell morphology was not abnormal, and the tidal line was complete. Compared with the KOA-model group, the Mankin’s score, the integrated optical density(IOD) value of HIF-1α and matrix metalloproteinase-1 (MMP-1) yellow dye granules, the expression of HIF-1α and vascular endothelial growth factor(VEGF) protein in each dose groups of Huangqibiejia pills were significantly lower than those in the KOA-model group (P<0.05). The expression levels of glucose transport-1(Glut-1) and MMP-1 in cartilage of rats in high dose group were lower than those in KOA-model group (P<0.05). Conclusion Huangqibiejia pills can reduce the degree of cartilage injury and inflammation in KOA model rats, and the mechanism is related to the regulation of Glut-1, VEGF and MMP-1 expression by HIF-1α.