Abstract： Objective:To observe Notch1 inhibitor[3, 5-Difluorophenacetyl-L-alanyl-S-phenyl glycine-2-butyl Ester(DAPT)]on diabetic peripheral neuropathy(DPN)rats and its possible mechanism.Methods:A total of 24 healthy 6-week-old male SD rats with a body mass of(210±10)g and a body mass range of 200 to 220 g were selected from the Endocrine Laboratory of The Affiliated Hospital of Jining Medical College.The rats were randomly divided into the conventional group, the DPN group and the DAPT group, with 8 rats in each group.One week after the SD rats were adaptively fed, the DPN group and the DAPT group of rats were each injected with streptozotocin(STZ)at a standard intraperitoneal dose of 65 mg/kg, and a diabetes model was established.The conventional group of rats were intraperitoneally injected with equal volume sodium citrate buffer.After 3 days, random blood glucose of tail vein ≥ 16.7 mmol/L was measured, which proved that STZ injection was successful.After further detection, blood glucose ≥ 16.7 mmol/L was measured and continued until the end of the experiment.Two weeks after the establishment of diabetic rat model, rats in the DAPT group were intraperitoneally injected with 0.1 mg/(kg·d)DAPT for 3 consecutive days.All rats’ sciatic nerve conduction velocity and pain and temperature thresholds were detected, and the expressions of Notch1 and Ras homologous family kinases(ROCK)1 and ROCK2 were detected.Results:The blood glucose of DPN group at 7 days[(17.63±0.41)mmol/L], 14 days[(17.95±1.22)mmol/L], 30 days[(20.81±3.21)mmol/L]and 60 days[(26.08±3.56)mmol/L]in DPN group were higher than those in conventional group[(6.35±0.72)mmol/L, (6.33±0.62)mmol/L, (6.05±0.74)mmol/L, (7.54±0.65)mmol/L]. The blood glucose level in the DAPT group[(21.17±1.44)mmol/L]was lower than that in the DPN group[(26.08±3.56)mmol/L]. The body mass of DPN group at 30 days[(217.61±18.35)g]and 60 days[(200.75±13.19)g]was less than that of conventional group[(308.25±16.72)g, (344.13±15.34)g]. The results showed that the sciatic nerve conduction velocity in the DPN group[(36.25±2.82)s]was slower than that in conventional group[(50.25±1.67)s]; the sciatic nerve conduction velocity in the DAPT group[(40.63±3.70)m/s]was faster than that in the DPN group[(36.25±2.82)m/s]; the thermal pain threshold of DPN group[(25.50±1.60)s]was higher than that of conventional group[(14.13±1.25)s]; the thermal pain threshold of DAPT group at 60 days[(17.25±1.67)s]was lower than that of DPN group[(25.50±1.60)s], and the differences were statistically significant( P<0.05). The proportion of myelin sheath in DPN group was higher than that in conventional group, and that in DAPT group was lower than that in DPN group; the average immunofluorescence density of Notch1 in DPN group was significantly higher than that in conventional group, and that in DAPT group was significantly lower than that in DPN group; the average immunofluorescence density of ROCK1 in DPN group was significantly higher than that in conventional group, while that in DAPT group was significantly lower than that in DPN group; the average immunofluorescence density of ROCK2 in DPN group was significantly higher than that in conventional group, while that in DAPT group was significantly lower than that in DPN group( P<0.05). Conclusion:Notch1 inhibitor DAPT may have a protective effect on DPN by down-regulating ROCK.