Objective：To investigate the effects of transcription factor 7 like 2（TCF7L2） down-regulation on proinsulin levels and to explore the mechanism of TCF7L2 regulating proinsulin levels though proprotein convertase（PC）. Methods：Beta-TC-6 cells were cultured in vitro. TCF7L2 expression was down regulated by siRNA. There were three groups：blank control，scrambled control，and TCF7L2 interference group. QRT-PCR and Western blot were used to detect the mRNA and protein levels of TCF7L2，PC1 and PC2. Cell culture medium was collected and changes in insulin and proinsulin levels under basic and glucose stimulated conditions were detected by ELISA. Results：At 48 h after lentivirus infection of Beta-TC-6 cells，the infection rate achieved more than 95% under fluorescence microscopy. Compared with those of blank control group，the interference efficiency of mRNA was about 75%（0.25±0.03 vs. 0.97±0.11，P=0.000） and the interference efficiency of protein level was 50% in TCF7L2 interference group（0.29±0.08 vs. 0.57±0.09，P=0.008）. Compared with those of scrambled control，the TCF7L2 interference group had significantly lower levels of in－sulin（7.47±0.21） mU/L vs. （10.53±0.38） mU/L（P=0.000），but higher levels of proinsulin（10.73±0.51） pmol/L vs. （7.81±0.29） pmol/L（P=0.001） and lower mRNA and protein levels of PC1 and PC2（P<0.05）. Conclusions：TCF7L2 interference might affect the process and levels of proinsulin by decreasing the expression of PC.