Abstract: 　Objective　To explore the effect of erythromycin on glutathione hormone (GSH) and γ-glutamyl cysteine synthetase (γ-GCS) in premature newborn rats exposed to hyperoxia, to study the intervention effect of erythromycin on hyperoxia-induced lung injury. Methods One-day old preterm SD rats were randomly divided into four groups: control group, erythromycin group, hyperoxia group, erythromycin + hyperoxia group. Hyperoxia group and hyperoxia + erythromycin group were continuously exposed to oxygen (oxygen concentration > 0.85), control group and erythromycin group were in room air. Via caudal vein, the preterm rats was injected with erythromycin in erythromycin group and hyperoxia + erythromycin group, sodium chloride in control group and hyperoxia group daily. After 1,7,14 day(s) of hyperoxia (or air ) exposure, the preterm SD rats of four groups were killed, whole lung of these rats were isolated and histological changes were observed by hematoxylin -eosin (HE) staining, GSH and γ-GCS of pulmonary tissue homogenate were detected by Double antibody sandwich enzyme linked immunosorbent assay. Total lung RNA was extracted and γ-GCS mRNA was detected by reverse transcription polymerase chain reaction. Results The results showed that: After 1 and 7 day(s) of exposure, the expression of GSH、γ-GCS and γ-GCS mRNA in four groups showed significant differences（P<0.05）. Among them, GSH expression in erythromycin + hyperoxia group was higher than that in the other three groups in 1,7,14 day(s) of exposure with significant differences (P<0.05); GSH expression in erythromycin + hyperoxia group and hyperoxia group reached the peak after 7 days of exposure. The expression of γ-GCS and γ-GCS mRNA in erythromycin + hyperoxia group and hyperoxia group were higher than the other two groups after 1and 7 day(s) of exposure, the expression of γ-GCS mRNA in erythromycin + hyperoxia group were higher than that of hyperoxia group with significant differences (P<0.05). Conclusions The expressions of GSH and γ-GCS in the lung of premature SD rats were abnormal by oxidation outbreak. Erythromycin may increase the activity of γ- GCS, improve the anti-oxidation ability of GSH, and alleviate hyperoxia mediated lung injury in premature rats.