OBJECTIVE： To observe clinical efficacy and safety of naloxone hydrochloride combined with Danshen injection in the treatment of neonatal hypoxic ischemic encephalopathy （HIE）. METHODS： 104 patients with HIE were randomly divided into observation group and control group with 52 cases in each group. The control group was treated with Naloxone hydrochloride injection 0.02 mg/kg，ivgtt，qd and conventional symptomatic treatment； while observation group was additionally treated with Danshen injection 4-6 ml+10％ Glucose injection 20 ml， ivgtt， qd， on the basis of the control group. Treatment course of 2 groups lasted for 7 d. Clinical efficacy， symptom and sign recovery of 2 groups were compared， as well as levels of serum MMP-9， IL-6 and TNF-α， cerebral hemodynamic parameters and ADR. RESULTS： There was no statistical significance in MMP-9，IL-6，TNF-α and cerebral hemodynamic parameters before treatment （P＞0.05）. The total effective rate of observation group （92.31％） was significantly higher than that of control group （75.00％）； after treatment， the recovery time of consciousness disturbance， primitive reflex and muscle tension in the observation group were shorter than those in the control group； the levels of serum MMP-9， IL-6 and TNF-α in observation group were significantly lower than those in control group； peak systolic flow velocity （PSFV）， end-diastolic flow velocity （EDTV） were higher in the observation group than in the control group， with statistical significance （P＜0.05）； resistance index （RI） was lower than in control group， but without statistical significance （P＞0.05）. No ADR was observed in 2 groups. CONCLUSIONS： Naloxone hydrochloride combined with Danshen injection can significantly promote HIE and signs recovery， reduce the levels of serum MMP-9， IL-6 and TNF-α， and improve hemodynamic parameters with good safety.