Introduction: Electro-acupuncture (EA) can significantly improve inflammatory response, but the specific mechanism is not clear. Limb ischemia-reperfusion (I/R) first produces inflammatory reactions in the lungs. In this study, EA on Zusanli (ST36) and Sanyinjiao (SP6) were used to explore the mechanism of improving tissue inflammation by sciatic nerve disconnection. Material and Methods: A total of 56 male Sprague-Dawley rats were randomly divided into sham group, model group, EA group, SEA group, SNC+EA group, TNC+EA group and PNC+EA group. The sham groups were not given any treatment. Rats in the model group were treated with limb I/R without acupuncture intervention. In the EA group, ST36 and SP6 were given EA treatment for 30min before modeling. No electric current was given in the SEA group, and other operations were the same as those in the EA group. The SNC+EA group, TNC+EA group and PNC +EA group were respectively given sciatic nerve, tibial nerve or peroneal nerve amputation 72h before modeling, and the others were the same as the model group. Results: Compared with the sham group, PaO2 and a/A ratios decreased significantly in the model group (P <0.05), while PA-aO2, RI, the ratio of wet to dry, lung injury value and inflammatory factor TNF-α, IL-1, IL-6, and MPO increased significantly (P <0.05). Compared with the model group, PaO2, a/A ratios increased significantly in the EA group (P <0.05), while PA-aO2, RI, the ratio of wet to dry lung, lung injury value, and TNF-α, IL-1, IL-6, and MPO decreased significantly (P <0.05). After transection of the sciatic nerve, the protective effect of EA disappeared. However, when the peroneal or tibial nerve was severed, EA continued to maintain the protective effect. Conclusion: EA on ST36 and SP6 can alleviate lung injury caused by limb I/R through the sciatic nerve.