Objective To explore the effect of fasudil on diabetic peripheral neuropathy (DPN) rats and its possible mechanism. Methods Sixty SD rats were randomly divided into control group， model group， positive control group， fasudil low-dose group， and fasudil high-dose group， with 12 rats in each group. High-fat diet combined with streptozotocin was used to establish a diabetic rat model. After 8 weeks of administration， the fasting blood glucose and body weight of the rats were measured. Eddy hot plate method to detect thermal withdrawal latency (TWL). Paw-Withdrawal Threshold (PWT) detected by the Von Frey experiment. The Randall Selitto experiment detects mechanical allodynia (mechanical allodynia， MWT). Bipolar needle electrodes detect motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV). HE staining and toluidine blue staining were used to detect the pathological changes of sciatic nerve. The kit was used to detect the changes of MDA， GSH， SOD， IL-1β， IL-6 and TNF-α content. Western blot was used to detect the expression of Nrf2， HO-1， P-p65 and p65 protein.Results Compared with the control group， the weight， number of sciatic nerve axons， TWL， MWT， PWT， MNCV and SNCV of the model group were significantly reduced (P<0.05)， and blood glucose， the content of MDA， IL-1β， IL-6 and TNF-α， and the expression of p-p65/p65 protein were significantly increased (P<0.05)， and the content of GSH， SOD， and the expression of Nrf2 and HO-1 protein were significantly reduced (P<0.05). Compared with the model group， the weight and blood glucose levels of rats in the positive control group， low-dose fasudil group and high-dose fasudil group were not significantly different (P>0.05)， the number of sciatic nerve axons， TWL， MWT， PWT， MNCV and SNCV significantly increased (P<0.05)， the content of MDA， IL-1β， IL-6 and TNF-α and the expression of p-p65/p65 protein were significantly reduced (P<0.05)， the content of GSH， SOD and the expression of Nrf2 and HO-1 protein were significantly increased (P<0.05).Conclusion Fasudil may play a protective role in DPN rats by activating the Nrf2/ARE pathway and inhibiting the NF-κB pathway.