Objective This study examined the effects of repaglinide on the proliferation, differentiation, and apoptosis of mouse pre-osteoblasts MC3T3-E1 subclone 14 cell under high glucose condition.Methods MC3T3-E1 cells cultured in vitro for 48h were divided into the following groups: control group and repaglinide with different concentrations (0.01, 0.1, 1, and 10 μmol/L).Cell proliferation was measured by CCK-8 assay.mRNA levels of type I collagen(COL-Ⅰ), osteopontin(OPN) and alkaline phosphatase(ALP) were assayed using quantitative real-time PCR.Expression of apoptosis related proteins (Bcl-2, Bax) was measured by western blot analysis.Results (1)Compared with control group, the proliferation rate of repaglinide with different concentrations increased, while the proliferation rate of the 1 μmol/L repaglinide group significantly higher than that of the control group(P<0.05).(2) There was no significant difference on the COL-Ⅰ mRNA expression among the repaglinide groups and the control group(P>0.05).Compared with control group, the OPN and ALP mRNA expression increased significantly in the 1 μmol/L repaglinide group(P<0.05), while the OPN expression was significantly declined in the 10 μmol/L repaglinide group(P<0.05).(3)The protein expression of Bcl-2 was positively related with repaglinide concentration(P<0.05), while the protein expression of Bax went down in the 1 and 10 μmol/L repaglinide groups(P<0.05).Conclusion When exposed to high glucose concentration, repaglinide in a certain concentration range may promote the proliferation and differentiation of MC3T3-E1 subclone 14, while restrain its apoptosis.