Objective:To observe the effect of Qishen decoction on PI3K/Akt/mTOR signal pathway in rats with liver fibrosis;Methods:40 SD rats were randomly divided into four groups: the control group, the model group, Qishen decoction group, and Colchicine group. Except the control group, the remaining three groups were used to establish liver fibrosis model by intraperitoneal injection of carbon tetrachloride. At the end of modeling, Qishen decoction and colchicine group were given corresponding drug gavage treatment, rats in the model group and the control group were treated with equal volume distilled water for 8 weeks. At the end of the treatment, the blood and liver tissues of rats in each group were collected, the liver function indexes and hydroxyproline content were detected by ELISA, the pathological morphology of liver tissue was detected by HE and Masson staining. Immunohistochemical method was used to detect α-SMA protein expression and West blot was used to detect the expression of α-SMA, Col-I, Col-Ⅲ and key proteins in PI3K/Akt/mTOR signaling pathway.Results: Compared with the model group, Qishen decoction significantly reduced the levels of AST, ALT, and TBIL in serum, and reduced Hyp content, inflammatory score, fibrosis score, and collagen staining area in liver tissue, differences were statistically significant (P<0.05). At meanwhile, Qishen decoction significantly reduce the expression level of α-SMA, CoL-I and Col-Ⅲ in liver tissue(P<0.05). In addition, compared with the model group, Qishen decoction significantly down-regulated the expressions of p-PI3K, p-Akt and p-mTOR in liver tissue, difference were statistically significant (P<0.05).Conclusion: Qishen decoction suppresses liver fibrosis and inhibits the deposition of collagen in liver tissue by down-regulating PI3K/Akt/mTOR signal pathway.