〔Abstract〕 Objective To observe the effect of angiotensin(1-7) [Ang(1-7)] on the apoptosis and angiogenesis of fibroblasts in the oral submucosal fibrosis(OSF), and to explore the effect preliminarily mechanism. Methods Fibroblasts were isolated and cultured from human buccal mucosal tissue, the cell morphology was observed by inverted microscope, and the expression of vimentin was detected by immunofluorescence staining; areca nut extract(ANE) was used to induce human fibroblasts to simulate the in vitro model of fibroblasts in OSF, the experimental groups included control group(normally cultured cells), ANE group(100 μg/ml ANE cultured cells for 48 hours), ANE+low-dose Ang(1-7) group(100 μg/ml ANE+10-7 mol/L Ang(1-7) cultured cells for 48 h), ANE+high-dose Ang(1-7) group(100 μg/ml ANE+10-5 mol/L Ang(1-7) cultured cells for 48 h), immunofluorescence staining detected the expression of α-smooth muscle actin(α-SMA), ELISA method detected the content of Collagen I and Collagen Ⅲ in the cell culture supernatant, MTT method detected cell proliferation activity, flow cytometry detected cell apoptosis, the tubule formation experiment detected the vascularization of human umbilical vein endothelial cell(HUVEC); After the mRFP-GFP-LC3 virus was transferred to the cells, the level of autophagy was detected by immunofluorescence staining,Western blot detected the expression of autophagy-related protein Beclin-1 and the ratio of LC3-Ⅱ/LC3-Ⅰ. Results The isolated and cultured cells were in a long spindle shape,and Vimentin was positively expressed,indicating that fibroblasts were successfully isolated; Compared with the ANE group,the fluorescence expression of α-SMA protein in ANE low dose Ang(1-7) group and ANE + high dose Ang(1-7) group significantly decreased,the contents of Collagen I and Collagen Ⅲ in the culture supernatant were reduced(P<0. 05),cell proliferation activity decreased(P<0. 05),and cell apoptosis rate increased(P<0. 05),the cell culture supernatants of the two groups inhibited the angiogenesis of HUVEC(P<0. 05),endophagosomes were reduced(P<0. 05),Beclin-1 protein expression was reduced(P<0. 05),and the ratio of LC3-Ⅱ/LC3-Ⅰ was down-regulated(P<0. 05); in addition,the effect of ANE + high-dose Ang(1-7) group was stronger than that of ANE + low-dose Ang(1-7) group(P<0. 05). Conclusion Ang(1-7) can inhibit the activation of fibroblasts induced by ANE,promote cell apoptosis,and reduce the angiogenesis of HUVEC,this mechanism may be related to the regulation of cell autophagy.