The PI3K/AKT signaling pathway is an essential mechanism by which cells regulate oxidative stress effect and induces HSC activation and proliferation dependent on HIF-1α in response to hypoxia. Here, we analyzed whether PI3K/AKT signaling is associated with PPARγ inhibition of hypoxia-induced HSCs activation. Results showed that hypoxia-induced HSCs activation when AKT phosphorylation was significantly enhanced (Figure 3(c)). Inhibition of PI3K with LY294002 (20 μM) distinctly opposed the above-mentioned activation. Simultaneously, PPARγ expression was also recovered (Figures 3(c) and 3(d)). Similarly, activation of PI3K with 740 Y-P (25 μg/ml) of HSCs exposed to hypoxia in the presence of RSG (50 nM) significantly reduced PPARγ expression, along with increased level of α-SMA and desmin (Figures 3(a) and 3(b)). These results imply that PI3K/AKT signaling blocked the inhibitory effect of PPARγ on hypoxia-induced activation of HSCs.