In a previous study, we showed that octreotide alleviate hepatic fibrosis. However, its underlying molecular mechanisms are still poorly understood. In the current study, rats with CCl 4 -induced liver injury and Hepatic Stellate Cells (HSCs) were employed for in vitro and in vivo studies to observe the effects of octreotide on progression of liver fibrosis. The results in rats indicated that octreotide remarkably alleviated hepatic injury. The treated rats showed improved pathological manifestations and reduced liver indicators, e.g., liver weight, liver index and liver hydroxyproline (Hyp) content. Additionally, activities of serum total bilirubin (TBIL), aspartate transaminase (AST) and alanine transaminase (ALT), and serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP) also decreased. Furthermore, releasing inflammatory factors and proliferation of activated HSCs under different treatments were detected in which levels of IL-1β, IL-6, TNF-α decreased and hepatocytes proliferative capacity reduced through Bcl-2/Bax-dependent apoptosis. Finally, our results demonstrated that octreotide was able to exert an inhibitory effect on the activation of HSCs regulating the PI3K/AKT signaling pathway. In summary, our study corroborated that octreotide could prevent liver fibrosis probably via modulating Bcl-2/Bax and PI3K/AKT signaling pathway. • Octreotide inhibited Bcl-2/Bax and PI3K/AKT signaling pathway and CCL 4 -induced hepatic fibrosis. • Octreotide decreased hepatocyte apoptosis in CCl 4 -induced liver fibrosis and promoted activated HSCs apoptosis. • Octreotide inhibited inflammation response and hepatic stellate cells proliferation. [ABSTRACT FROM AUTHOR]