Abstract: Objective To observe and explore the effectiveness of aminophylline (Ami) combining with naloxone(Nal) for neonatal severe disease and respiratory depression. Methods Total 84 Neonatal severe disease and respiratory depression accepted drug treatment in this hospital during June,2013 to June,2015 were selected,and were divided into two groups accorded to the random number method,42 cases in each group, the control group was treated with Oral Ami, while the observation group was treated with Nal on the basis of the control group.Respiratory rate (RR),end-tidal CO₂ pressure (PetCO₂) and pulse oximetry (SPO₂) before and after treatment as well as incidence of adverse reactions were recorded and compared,and comprehensive efficacy were evaluated. Results The difference of RR,PetCO₂ and SPO₂ before treatment was not statistically significant(P>0.05);after treatment,RR,PetCO₂ and SPO₂ in the observation group were (15.2±1.8) times/min,(42.7±5.2) mm Hg (1 mm Hg=0.133 kPa) and (99.3±1.3)%,while was (12.4±1.3) times/min,(48.5±5.8) mm Hg and (99.6±0.9)% in the control group,RR in observation group were significantly higher than the control group,while PetCO₂ were significantly lower than the control group(P<0.05);total effective rate was 88.0%(37/42) in observation group,while was 69.0%(29/42) in the control group, the difference was statistically significant(P<0.05);the difference of adverse reactions incidence between the two groups was not statistically significant(P>0.05). Conclusion Ami and Nal can improve respiratory depression in neonatal intensive disease and respiratory depression, the effect is significant, and no significant side effects,thus it is a safe and effective solution for the Neonatal severe disease and respiratory depression.