Abstract: Objective To observe the change in phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway in rats with hepatic fibrosis induced by porcine serum immunization and to explore the effect of blueberry on the change of the signaling pathway.Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into a normal control group,a hepatic fibrosis model group,three blueberry treatment groups (at dosages of 0.25,0.50,and 1.00 ml juice/100 g body weight by gavage daily),and a Compound Biejiaruangan Troche (CBT,an traditional Chinese patent medicine made mainly of Carapax Trionycis,Panax notoginseng,Radix Paeoniae Rubra,Ophiocordyceps sinensis,and Forsythia suspense,at dose of 0.054 g/100 g body weight by gavage daily).All the rats,except for those of the normal control group,were injected intraperitoneally with porcine serum twice a week(on second and fifth weekday)for 12 weeks to establish hepatic fibrosis model;the rats of blueberry and CBT group were administered,respectively,with blueberry juice and CBT simultaneously.All the rats were sacrificed by the end of 12-week treatment.Liver index,serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.Pathological changes in the hepatic tissue were observed with hematoxylin-eosin (HE) staining.The expression of protein kinase B (Akt1) and phosphorylated Akt1 (p-Akt1) were detected with immunohistochemistry and Western blot.Results Compared with in the normal control group,the liver index (0.58±0.02) increased significantly (P<0.01) and liver fibrosis was obvious in the liver fibrosis model;while,the liver index (0.37±0.06) was significantly lower (P<0.01)and liver fibrosis was alleviated in the blueberry treatment groups compared to those in the liver fibrosis model group.Compared with hepatic fibrosis model group,the expression of Akt1 (0.99±0.09) and p-Akt1 (0.81±0.06) were significantly increased in the liver fibrosis model group (both P<0.01) compared to those in the control group;whereas the expressions of Akt1 (0.39±0.13 and 0.42±0.15) and p-Akt1 (0.44±0.06 and 0.43±0.12) were significantly decreased in the moderate and high dose blueberry treatment groups compared to those in the liver fibrosis model group (both P<0.01).Conclusion Blueberry can impact the development of immune hepatic fibrosis in rats and the effect may be related to the activation of PI3K/Akt signaling pathway.