AIM To explore the exact interaction between Notch and transforming growth factor (TGF)-beta signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells (PBMCs) were isolated from the modeled rats, and cultured with.-secretase inhibitor DAPT and TGF-beta inhibitor for 24 h. The mRNA levels of Notch and TGF-beta signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-beta proteins was analyzed by western blotting. RESULTS Compared to control rats, Notch and TGF-beta signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-beta inhibitor suppressed Notch and TGF-beta signal transducer in PBMCs of model rats. DAPT reduced mRNA and protein expression of TGF-beta signaling, such as TGF-beta 1 and Smad3. TGF-beta inhibitor also downregulated Notch1, Hes1 and Hes5, and mRNA and protein expression of the Notch signaling pathway. CONCLUSION Notch and TGF-beta signaling play a role in liver fibrosis. TGF-beta signaling upregulates Notch signaling, which promotes TGF-beta signaling.