Objective To observe the effect of quercetin on mechanical allodynia, astrocyte activation, and upregulation of pain-related transient receptor potential vanilloid 1 (TRPV1) and P2X purinoceptor 3 (P2X3) in mice with paclitaxel-induced peripheral neuropathy. Methods Twenty-four C57BL/6 mice were divided randomly into control, model, and model + quercetin groups (n=8 mice per group). Paclitaxel (total dose 8 mg/kg) was injected intraperitoneally into mice in the model and model + quercetin groups to establish the model. Mice in the control group were injected intraperitoneally with the same volume of vehicle. On day 8 after the first injection, mice in the model + quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle. Mechanical pain was measured by the von Frey test. Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence. Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot. Results (1)Compared with model group, the mechanical pain of mice in model + quercetin group were relieved.(2)Compared 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). Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy. This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.