Objective To monitor the levels of NO and IL-18 in neonatal hypoxic-ischemic encephalopathy (HIE), to explore the relation of NO, IL-18 and HIE. Methods HIE infants admitted in our hospital from January to Novermber of 2007 were taken as observation group and normal neonates were chosen as control group. In each group,the concentrations of NO and IL-18 were tested on 1 day,3 days,7 days and 14 days. Results On the first day after birth,the levels of serum NO and IL-18 in control group were (6.40±4.24) μmol/L and (2.84± 2.53)ng/L,in mild HIE group were (21.55±7.23) μmoL/L and (6.79±1.96) ng/L,in moderate HIE group were (33.38±2.81) μmol/L and (14.07±2.91) ng/L,in severe HIE group were (66.39±18.03) μmoL/L and (26.85±9.82) ng/L. The levels of serum NO and IL-18, in HIE groups were higher than those in control group (P<0.01), were much higher in patients with moderate and severe HIE than those with mild HIE (P<0.01). On 14 days,the levels of serum No and IL-18 were not different in moderate HIE groups and those in the control group (P>0.05), butwere higher in the severe HIE groups than those in the control group [NO and IL-8 level: (5.38± 4.79) μmol/L and (2.39±1.41) ng/L in control group and (24.89±9.43) μmol./L and (13.43±3.23) ng/L in severe HIE group(P<0.01)]. Conclusion NO and IL-18 are involved in the whole course of HIE, which are correlated with the severity of condition. They may be acted as indicators in monitoring pationts' conditon.