Abstract: Objective To investigate the role of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in moderating effect of astaxanthin on the activation of human hepatic stellate cells (LX-2 cell).Methods LX-2 cells were divided into a control group,three astaxanthin groups at the dosages of 5,10,and 20 μmol/L,and inhibitor group (25 μmol/L LY294002),and an inhibitor plus astaxanthin group (25 μmol/L LY294002 and 20 μmol/L astaxanthin).The mRNA expressions of α-smooth muscle actin (α-SMA) and collagen I (col1a1),and protein expression of Akt,phosphorylated Akt (p-Akt) in LX-2 cells were detected 48 hours after the treatments.Results The mRNA expressions of α-SMA and col1a1 in LX-2 cells of astaxanthin groups were obviously decreased in a dose-response manner compared with those of the control group (both P<0.05).The protein expression of p-Akt (0.42±0.05) and mRNA expressions of α-SMA (0.23±0.05) and col1a1 (0.35±0.06) in LX-2 cells of inhibitor group were obviously reduced compared to those of the control group (all P<0.05);the protein expression of p-Akt (0.60±0.07) and mRNA expressions of α-SMA (0.48±0.07)and col1a1 (0.61±0.04) in LX-2 cells of astaxanthin groups were obviously decreased compared to those of the control group (all P<0.05);the protein expression of p-Akt (0.18±0.04) and mRNA expressions of α-SMA (0.11±0.05) and col1a1 (0.20±0.03) in LX-2 cells of inhibitor plus astaxanthin group were obviously reduced compared with those of the inhibitor group (all P<0.05).Conclusion Astaxanthin can restrain the activation of hepatic stellate cells through the PI3K/Akt signaling pathway and play an important role in inhibiting the occurrence of fibrosis in non-alcoholic fatty liver disease.