Objective To investigate the effect and potential mechanism of Taohong Siwu decoction(THD) on paclitaxel-induced peripheral nerve injury in rat. Methods Twenty-four female SD rats were randomly divided into control group, model group, THD low-dose group and THD high-dos group (6 each). Rats in control group were given saline of the same volume, while paclitaxel (8 mg/kg) was slowly injected intraperitoneally into rats in other three groups on the 1, 3, 5, and 7th day for 4 times. Rats with mechanical withdrawal threshold under 4 g indicated model success. The THD low-dose group and THD high-dose group was given 1 g/ml or 2 g/ml of THD 2 times/d, for 4 weeks. The threshold of mechanical stimulation, cold and hot stimulation to rats was detected after administration. The pathological morphology of sciatic nerve was observed by HE staining.The contents of inflammatory factor Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), thiobarbituric acid reactive substances (TBARS) and L-Glutathione (GSH) in the sciatic nerve were measured with automatic biochemical analyzer.The relative contents of myelination pieces were determined by red oil O staining and expression level of autophagy associated proteins microtubule-associated protein 1 light chain3-I (LC3-I), LC3-Ⅱ, and Beclin1 were detected by Western blotting. Results Compared with control group, rats in model group showed lower threshold to mechanical stimulation and lower sensitivity to hot and cold stimulation (P<0.05), expression levels of IL-6, TNF-α and TRABS elevated (P<0.05), while GSH levels decreased (P<0.05). HE staining showed tissue injury, atrophy, inflammatory infiltration, and myelination pieces increased significantly and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 reduced (P<0.05). The results of THD low-dose group and THD high-dose group showed that the response of rats to mechanical stimulation, hot and cold stimulation was obviously improved (P<0.05), levels of IL-6, TNF-α and TRABS significantly decreased (P<0.05), while level of antioxidant GSH significantly elevated (P<0.05). Compared with THD low-dose group, rats in THD high-dose group showed elevated threshold to mechanical stimulation and more sensitive to mechanical stimulation, hot and cold stimulation (P<0.05), myelination pieces decreased significantly (P<0.05) and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 increased (P<0.05). Conclusion Taohong Siwu decoction can alleviate rat peripheral nerve injury caused by paclitaxel, and its mechanism may be related to reducing inflammatory reaction and inducing autophagy to remove damaged debris.