Objective To explore the possible mechanism of Bushen Huoxue Decoction（补肾活血汤） in the treatment of steroid-induced osteonecrosis of the femoral head（SONFH）. Methods Thirty-two SD rats were randomised into control group

model group

Bushen Huoxue Decoction group and antagonist group

with eight rats in each group. The rats in all the groups except for control group were injected with twice of endotoxin（20μg/kg） in the tail vein and three times of prednisone（40 mg/kg） in the hip muscles

with an interval of 24 hours each time to prepare the SONFH rat model. Twenty-four hours after the last intramuscular injection

rats in Bushen Huoxue Decoction group were administered with 6.3 ml/（kg·d） of Bushen Huoxue Decoction by gavage; same amount of normal saline was given to the control group and the model group by gavage; and JNJ-31020028（10 mg/kg） was subcutaneously injected to the antagonist group; all the interventions were administered three times per week

for eight weeks.The pathological changes of the femoral head were assessed by HE staining

and percentage of empty lacuna and bone trabecular area were calculated; ELISA method was used to assess the content of hypothalamic neuropeptide Y（NPY）

Y2 receptor（Y2 R）

femoral head NPY and Y1 receptor（Y1 R）; Western Blot method was used to detect the expression of hypothalamic and femoral head NPY

femoral head B-cell lymphoma 2（Bcl-2）

and Bcl-2 related x protein（Bax）. Results The HE staining results showed that the bone trabecula was sparse and damaged in the model group

with empty bone lacuna and fat vacuoles commonly seen. The pathological damages were significantly reduced in Bushen Huoxue Decoction group and antagonist group. Compared to the model group

Bushen Huoxue Decoction group and antagonist group had lower percentage of empty bone lacuna and larger bone trabecular area（P<0.01）. Compared to the control group

the model group had increased levels of hypothalamic NPY

Y2 R

femoral head NPY and protein expression

as well as decreased Bcl-2 and increased Bax（P<0.05 or P<0.01）. Compared to model group

Bushen Huoxue Decoction group and antagonist group had lower hypothalamic NPY

Y2 R content and protein expression

higher femoral head NPY and protein expression

as well as higher Bcl-2 and lower Bax（P<0.01）. Conclusion Bushen Huoxue Decoction can reduce the pathological damages of femoral head in SONFH rats

which may be related to its function of inhibiting hypothalamic NPY and Y2 R

promoting NPY expression in bone tissues

and increasing anti-apoptotic ability of bone tissues.