Objective: To observe the effects of moxibustion at Huantiao (GB30) acupoint on nerve repair, regeneration, and function in rats with sciatic nerve injury (SNI), and explore the possible mechanism of SNI improvement via moxibustion. Methods: A total of 70 specific pathogen-free (SPF) grade male Sprague-Dawley (SD) rats were randomly assigned to control group (n = 10) and model group (n = 60). Following replication of SNI to model group rats, 60 SNI model rats were randomly allocated to SNI groups of 1 d, 3 d, and 7 d and moxibustion groups of 1 d, 3 d, and 7 d with 10 rats in each group. Moxibustion groups were given moxibustion at the Huantiao (GB30) acupoint on the affected side with a 5 cm distance from the skin under isoflurane respiratory anesthesia and treated once a day for 20 min for 1 d, 3 d, and 7 d, respectively. Control and SNI groups were anesthetized with isoflurane daily for 20 min. Open field tests and thermal pain threshold tests were conducted, and the general condition of rats was observed in each group pre-modeling and on treatment day 1, 3, and 7. At the end of the treatment, immunofluorescence was used to detect the axonal growth rate, axonal growth density, and Schwann cells (SCs) proliferation in the middle 1-mm cross-section of the crush injury segment in rats. The gastrocnemius muscles on both sides of the rats were taken and weighed to calculate the wet weight ratio of the gastrocnemius muscles on both sides to observe the muscle atrophy of the rats, and hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of the gastrocnemius muscles on the affected side. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression levels of nerve growth factor (NGF), interferon (IFN), macrophage migration inhibitory factor (MIF), interleukin (IL)-4, and transforming growth factor (TGF)-β in the sciatic nerve tissue of the rats. Results: After modeling, rats in both moxibustion and SNI groups showed typical signs of pain behaviors (bending and curling of the hind soles of the affected side, licking claws, and lameness) and decreased activity compared with control group. The main benefits of moxibustion were evident from day 3: compared with SNI group, rats in moxibustion group had marked relief of pain behavior, increased activity levels and movement, and a lower response to thermal pain. At the same time, moxibustion significantly promoted the repair of SNI, as evidenced by the significantly better axonal growth rate, growth density, and SCs proliferation density in the crush injury segment compared with SNI group (P < 0.01). Moxibustion also regulated the local microenvironment of the injury, up-regulated the pro-nerve repair factors NGF, IL-4, and TGF-β (P < 0.05), and down-regulated the pro-inflammatory factors IFN-γ (P < 0.01) and MIF (P < 0.05). By day 7, the histomorphology of the gastrocnemius muscle in moxibustion group was improved, as indicated by enlarged muscle fibers, elevated regular myocyte morphology and wet weight ratio of the affected and unaffected sides (P < 0.05), as well as a sustained high expression levels of NGF, IL-4, and TGF-β (P < 0.05, P < 0.05, and P < 0.01, respectively), and a maintenance of low level of IFN-γ (P < 0.01). Concurrently, the MIF level was not significantly different from SNI group (P > 0.05). Conclusion Moxibustion at the Huantiao (GB30) acupoint effectively improves motor function and promotes recovery of sensory function and nerve regeneration in SNI rats, which may be related to the regulation of local inflammatory response, the promotion of nerve growth factor expression, the improvement of regenerative microenvironment, and the acceleration of SCs proliferation and axonal growth rate in damaged nerves.