Objective To evaluate the therapeutic effects of Gubitongxiao decoction on mice in a steroid induced femoral head necrosis model, and to investigate the underlying mechanism from the nuclear factor kB receptor activating ligand (RANKL) /receptor activator of NF KB(RANK) / osteoprotegerin (OPG) signaling axis. Method The animal model of steroid-induced osteonecrosis of the femoral head (SONFH) was established by intraperitoneal injection of lipopolysaccharide and gluteal muscle injection of prednisolone acetate, and after identification by nuclear magnetic resonance, 60 mice with successful modeling were divided into model group (MC), Gubitongxiao decoction group (GBTX) and tongluoshenggu capsule group(PC), 20 mice in each group, Another 12 normal mice were set as the blank control group (NC). Were taken under anesthesia after intragastric administration of the corresponding drugs for 12 weeks in the corresponding group. The general behavior of the mice in each group before and after treatment was observed; the content of bone alkaline phosphatase (BALP) and type I amino-terminal elongation peptide (PINP) of the mice in each group was detected by enzyme-linked immunosorbent assay (ELISA); The levels of RANK, RANKL, OPG, and phosphoinositide specific phospholipase C in each group were determined by Western blot and real-time PCR (RT qPCR) ,γ2（PLCγ2) , cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAP) proteins and gene expression levels. Result Magnetic resonance imaging showed that the left hip of the mice after modeling showed a high signal state; compared with the NC group, the BALP and PINP contents and OPG protein and gene expression levels in the bone tissue of the MC group were significantly decreased (P<0.01) , RANKL, PLCγ2, CTSK, TRAP protein and gene expression levels were increased (P<0.01); compared with the MC group, the BALP, PINP content and OPG protein and gene expression levels in the treatment group were increased (P<0.01), The protein and gene expression levels of RANK, RANKL, PLCγ2, CTSK, TRAP decreased significantly (P<0.01, P<0.05). Conclusion Gubitongxiao decoction may inhibit RANK, RANKL, and PLCγ2 by upregulating OPG expression. Expression of CTSK and TRAP, thereby improving the situation of necrosis of the femoral head.