Abstract: Objective :To explore the specific inhibitor LY294002 of the signaling pathway PI3K/AKT that increases sensitivity to the regular chemotherapeutic agent of cholangiocarcinoma. Methods :The inhibition of cholangiocarcinoma was detected when treated individually with 5-FU, MMC,or cele-coxib, and was compared to a combination of those drugs individually with LY294002.Under the sameconditions,the apoptosis ratio was detected using flow cytometry. Results :The phosphorylation in-hibitor LY294002 can increase sensitivity to 5- FU and MMC and also increase the apoptosis ratio invitro. Conclusion :The phosphorylation inhibitor LY294002 can significantly enhance sensitivity to thechemotherapeutic agent. Inhibition of the PI3K/AKT signaling pathway could have a synergistic effecton treatment of cholangiocarcinoma.