Peroxisome proliferator-activated receptor (PPAR)γ is a fundamental nuclear receptor that regulates lipid metabolism, insulin sensitivity, and fat deposition. It plays an extremely important role in liver physiological metabolism . However, increasing researches have implicated that PPARγ is a key mediator in HSC activation and phenotypic alteration, thus maintaining HSCs in a quiescent phase [6, 7]. Recently, oxidative stress is considered to be involved in HSC activation and hepatic fibrogenesis . A large amount of publications has also reported that HSCs exposed to hypoxia could be activated through HIF1α and its downstream target genes or signaling pathways [9–11]. Based on those evidences, we hypothesized that the effect of PPARγ on HSCs is the mechanisms underlying the role of hypoxia in liver fibrogenesis. In fact, PPARγ has been found to be regulated by hypoxia in several diseases. Wang et al. reported that hypoxia decreased UCP2 via HIF-1-mediated suppression of PPARγ, leading to chemoresistance of non-small cell lung cancer . Jiang et al. found that hypoxia inhibited PKG-PPARγ axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries . However, it is not clear whether these cellular events are associated with the pathogenesis of hepatic fibrosis and its key functionary mechanisms. We therefore performed in vivo and in vitro experiments to test the above hypothesis.