However, little is known regarding the effect of PPARγ on HSC activation and hepatic fibrosis under hypoxia stress. To elucidate the interrelationship and molecular mechanism between HSCs activation and PPARγ in hypoxic environment, we designed experiments both in vitro and in vivo. For this purpose, by exposing CCl4 modeling rats to hypoxic environment, we validated the hypothesis that hypoxic stress promoted hepatic fibrosis. Notably, expression of PPARγ was inhibited by hypoxia. Moreover, expression of two markers of fibrosis, α-SMA and desmin, significantly increased. To further explore the effects of PPARγ in hypoxia, RSG, a PPARγ agonist, was added to hypoxia exposed groups. As expected, hepatic fibrosis induced by hypoxia was ameliorated with increasing PPARγ level. These results were also confirmed by HSC experiments in vivo. Our findings confirmed that PPARγ antagonizes hepatic fibrosis caused by hypoxia stress through inhibiting HSCs activation.