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Objective:To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes. Methods:BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features,levels of collagen type Ⅰ and collagen type Ⅲ,and angiogenesis were measured. Results:In the 8th week,epithelium atrophy,collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week,hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type Ⅰ changed significantly as the diseases advanced (P < 0.05); however,collagen type Ⅲ was not statistically different. Conclusions:An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.