Oxidative stress is one of the major pathogenesis of chronic obstructive pulmonary disease(COPD).γ-Glutamylcysteine synthetase(γ-GCS)is one of the paramount antioxidant enzymes in COPD.Peroxisome proliferator-activated recep tor-gamma(PPARγ)is a iigand-activated transcription factor,which is activated by specific ligands such as rosiglitazone(RGZ),exerting multiple biological effects.PPARγ coactivator-1α(PGC-1α)is a PPARγ coactivator,which binds to PPARγ by induction of PPARγ ligands,co-activating PPARγ target genes.Growing evidence has suggested that PPARγ/PGC-1α can regulate multiple antioxidant genes.However,the effect of PPARγ/PGC-1α on γ-GCS during the development of COPD remains unclear.Here,we measured the expression levels of PPARγ,PGC-1α and γ-GCS,γ-GCS activity and reactive oxygen species(ROS)contents in lungs of rats treated by cigarette smoke(CS)+lipopolysaccharide(LPS)and CS+LPS+RGZ,as well as lungs of patients suffered from COPD.Compared with lungs from CS+LPS-treated rats,lungs of RGZ-treated rats demonstrated markedly lower ROS contents,and remarkable increase of γ-GCS activity and increase of the expression levels of PPARγ,PGC-1α,and γ-GCS.Furthermore,compared with controls,expression levels of PPARγ,PGC-1α,and γ-GCS significantly increased in the lungs of mild COPD patients,and progressively decreased in lungs of patients with moderate and severe COPD.γ GCS protein was positively correlated with FEV1%.PPARγ and PGC-1α proteins were positively correlated with γ-GCS activity and mRNA level.In conclusion,γGCS showed compensatory upregulation in the early stage of COPD,which progressively decompensate with increasing COPD severity.The activation of the PPARγ/PGC-1α pathway may protect against COPD progression by upregulating γ-GCS and relieving oxidative stress.