Objective: To observe the effect of quercetin on mechanical allodynia, activation of astrocytes and upregulations of pain-related TRPV1 and P2X3 in mouse with paclitaxel-induced peripheral neuropathy. Method: 24 C57BL/6 mice were randomly divided into Control group, Model group, Model+Quercetin group, 8 mice per group. A total dosage 8 mg/kg of paclitaxel were injected intraperitoneally into mice of Model and Model+ Quercetin group to establish the model. Mice in Control group were injected intraperitoneally with the same volume of vehicle. At the 8th day after 1st injection, mice in Model+Quercetin group were injected with 60mg/kg quercetin solution orally and mice in other group were also injected with the same volume of vehicle. Mechanical pain were measured with von Frey. Immunofluorescence was used to detect the activation of astrocytes in the spinal dorsal horn and. Immunofluorescence and western blot were used to measure the expressions of TRPV1 and P2X3 in DRGs. Results: ① Compared with Model group, the mechanical pain of mice in Model+ Quercetin group were relieved. ②Compared with Model group, the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of Model+Quercetin group were alleviated (p<0.05). Conclusion: Our result indicate that quercetin can significantly reduce mechanical pain of paclitaxel-induced peripheral neuropathy. This mechanism maybe related to alleviating activation of astrocytes in spinal dorsal horn and reducing expressions of TRPV1 and P2X3 in the dorsal root ganglia.