〔Abstract〕 Objective To evaluate the effect of melatonin on nocturnal exacerbation of neuropathic pain and to explore its mechanism through the specific silencing information regulator 1(SIRT1)-brain and muscle ARNT-like protein 1(BMAL1) pathway. Methods 96 SPF-grade male C57/B6 mice were randomly divided into three groups: the sham operation(S) group, the neuropathic pain model(NP) group and the NP model + melatonin treatment(10 mg/kg)(NP+M) group; preoperative experimental mice were placed in the environment of the specified light pattern; the environment of alternating 12 h light and 12 h darkness was used for at least two weeks, and natural time was converted into the time of the award(ZT), and the starting point of the light was ZT0; only the sciatic nerve was isolated in the S group, and the mouse NP model was prepared using chronic constriction injury(CCI) of the sciatic nerve in the NP group and the NP+M group, and the NP+M group was injected with melatonin after the operation; the expression levels of SIRT1, BMAL1, and glutathione peroxidase 1(Gpx1) were detected in the spinal cord at each time point at 14 d postoperatively by Western blot. Postoperative co-staining of SIRT1 in the dorsal horn of the spinal cord with the spinal cord neuronal marker neuron-specific nuclear protein(NeuN), the microglial cell activation marker ion-calcium-binding adapter molecule 1(iba-1), and the astrocyte marker glial fibrillary acidic protein(GFAP) was carried out by immunofluorescence and iba-1 was detected at each time point to determine the activation status of microglia. Results SIRT1, BMAL1 and Gpx1 decreased in NP group mice at 14 d ZT22 postoperatively compared to ZT10 time point in NP group(P<0.05); SIRT1 and BMAL1 were elevated in NP+M group at ZT14 time point compared to ZT14 time point in NP group(P<0.05), whereas Gpx1 was elevated at ZT18 time point(P<0.05). SIRT1 was co-expressed in the dorsal horn of the spinal cord and in microglia. Compared with ZT10 time point, microglia expression decreased in NP group mice at ZT22 time point 14 d after surgery(P<0.05); compared with ZT10 time point, there was no statistically significant difference in microglia expression in NP+M group mice at ZT22 time point 14 d after surgery. Conclusion Melatonin attenuates nocturnal exacerbation of neuropathic pain by a mechanism that may be related to activation of microglia SIRT1-BMAL1 pathway protein expression.