Abstract: Objective To investigate the effect of matrine（Mat） on the proliferation， apoptosis and PI3K/Akt pathway of retinoblastoma（Rb） cells. Methods Rb cell lines Y79 cells were cultured with different concentration of Mat（0.5， 1.0， 1.5g/L）. Cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry（stained with Annexin V-FITC/PI）. Apoptosis related genes Bax and Bcl-2， as well as the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） pathways protein， including p85α，p-Aktser473and Akt， were determined by Western blotting. Results Mat could inhibit cell proliferation and induce apoptosis in a dose-dependent manner， respectively. Moreover， Mat increased the expression of Bax， but decreased the Bcl-2 protein expression. Results of Western blotting showed that Mat decreased the level of PI3K p85α and phosphor-Akt. Conclusion Mat could inhibit the proliferation and induce the apoptosis of Rb cells， probably modulating by the PI3K/Akt pathway.