Objective To observe the regulating effect of Tangluoning （TLN） on MAPKs pathway and NF-κB pathway in sciatic nerve of diabetic peripheral neuropathy （DPN） rats. Methods 8 weeks old Sprague Dawley （SD） male rats of pathogen-free were selected. All the rats were fed adaptively for two weeks with routine diet firs before experiment. The rat model with hyperglycemia leading to DPN was induced by intraperitoneal injected with streptozocin （STZ） 60 mg/kg except the blank control group. Those with hyperglycemia were randomly divided into normal control group,model control group,positive control （a-lipoic acid） group,and TLN group,and then successively administrated for 8 weeks. TLN group were given by gavage once a day with TLN powder dissolved in distilled water 5 g/kg,positive control group were given by gavage once a day with a-lipoic acid 20 mg/kg,model control group were given by gavage once a day with equal amount of distilled water. During administration,blood glucose was dynamically monitored to ensure the success of diabetes model. After 8 weeks,Western Blot method was used to measure the expression of p-JNK,p-ERK1/2,NFκB,p-NFκB in sciatic nerve. Results The expression of p-p38,p46 JNK、ERK1/2 were similar in all groups. And the difference had no statistical significance （P > 0. 05）; compared with normal group,the expressions of p-p38 MAPK,p-p46 JNK,p-ERK1/2,and p-NFκB were increased in model control group （P < 0. 01）. Compared with model group,the expressions of p-p38 MAPK,p-p46 JNK,p-ERK1/2,p-NFκB of a-lipoic acid group and TLN group were decreased （P < 0. 05）. Compared with normal group,the expressions of p-NFκB of model group were increased （P < 0. 01）; compared with model group,the expressions of p-NFκB of a-lipoic acid group and TLN group were decreased （P < 0. 05）. Conclusion Tangluoning can regulate MAPKS signaling pathway and NFκB signaling pathway so as to improve oxidative stress and avoid nerve injury.