Objective To determine the role of Bmi-1 in the submandibular gland (SMG) of mice.Methods SMG of 4-week wild-type(WT) and Bmi-1 null(Bmi-1-/-) mice was analyzed on the weight,salivary flow rate,hematoxylin-eosin staining morphological differences and the changes in proliferation and aging by histology,immunohistochemistry and Western blotting.Results Compared with WT mice,the average static salivary flow rate [WT:(0.21 ±0.02) μg/min,Bmi-1-/-:(0.10 ±0.02) μg/min] (P =0.001) and the submandibular gland weight [WT:(1.89 ± 0.15) μg],Bmi-1-/-:[(1.34 ± 0.07) μg] (P =0.003) of the male Bmi-1-/-mice were significantly decreased,the number of gland duct increased,and the granular convoluted duct showed reduced diameter and branches.More senescence-associated β-galactosidase positive cells existed in SMG of Bmi-1-/-mice (WT:0.00,Bmi-1-/-:0.18 ± 0.02),and Ki-67 immunopositive cells decreased in SMG of Bmi-1-/-mice(WT:0.40 ～ 0.47,Bmi-1-/-:0.18 ～ 0.20) (P =0.000).The expression of p16 (WT:1.00 ± 0.12,Bmi-1-/-:0.00 ±0.00) (P =0.003) and p19(WT:0.97 ±0.09,Bmi-1-/-:5.09 ±0.21) (P =0.004) were up-regulated dramatically in SMG of the Bmi-1-/-mice.Conclusions Bmi-1 gene deficiency causes abnormal function of SMG by inducing senescence phenotype of SMG.