Objective To investigate the effect of resveratrol (Res) on paclitaxel-induced neuropathic pain in rats by silent information regulator 2-related enzymes 1/peroxisome proliferator-activated receptor-gamma coactivator 1α (SIRT1/PGC1α) signaling pathway. Methods Fifty male Sprague-Dawley rats (weighing 180-200 g), after intrathecal intubation, were randomly assigned into five groups (n=10): control group (C group), paclitaxel group (P group), Res group (R group), Res pretreated group (R+ P group) and EX-527 (the specific inhibitor of SIRT1) + Res pretreated group (E+ R+ P group). Paclitaxel (2 mg/kg) was intraperitoneally injected on the 1st, 3rd, 5th and 7 day. Res (intraperitoneal injection, 40 mg/kg) and EX-527 (intrathecal injection, 10 μg/10 μl) were administered daily from the 1st day to the 14th day. We measured 50% paw withdrawal mechanical threshold (PWT) at three time points: 1 day before chemotherapy (T0), 8 days after chemotherapy (T1) and 14 days after chemotherapy (T2). The corpus striatum was harvested at the 15th day after paclitaxel intraperitoneal injection. Transmission electron microscope was applied to observe the mitochondrial histomorphology in five groups. The cell apoptosis in the corpus striatum was measured by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The expression of SIRT1 and PGC1α was detected using Western blotting. The levels of IL-1β and IL-10 in the corpus striatum were determined by enzyme linked immunosorbent assay (ELISA). Results At T2, as compared with C group (13.1±1.0), the PWT in P group and E+ R+ P group was decreased to (6.2±1.0) and (5.6±3.4) respectively (P<0.05); as compared with P group, the PWT in R+ P group was increased to (14.3±2.7) (P<0.05). In P group and E+ R+ P group, we observed swellings and vacuolations in the mitochondria, and these changes in R+ P group was alleviated. As compared with C group, the apoptosis cells in the corpus striatum were increased in P group (P<0.05), and they were significantly reduced in R+ P group as compared with P group (P<0.05). As compared with levels of SIRT1 (0.650±0.074) and PGC1α (0.590±0.057) in C group, the expression levels of SIRT1 and PGC1α in P group were decreased to (0.320±0.032) and (0.200±0.067) respectively (P<0.05); as compare with P group, the expression levels of SIRT1 and PGC1α in R+ P group were increased to (0.530±0.010) and (0.530±0.041) respectively (P<0.05). As compared with IL-1β (7.57±0.09) pg/ml and IL-10 (32.65±0.16) pg/ml in C group, the levels of IL-1β in P group were increased to (15.11±0.20) pg/ml (P<0.05), and those of IL-10 in P group were decreased to (12.92±0.17) pg/ml (P<0.05); as compared with P group, the level of IL-1β in R+ P group was significantly decreased to (9.42±0.13) pg/ml (P<0.05), and that of IL-10 in P group was significantly increased to (24.77±0.12) pg/ml (P<0.05). Conclusion Res alleviates paclitaxel-induced neuralgia, which is related with activation of SIRT1/PGC1α signaling pathway, reduction of cell apoptosis, inhibition of inflammation, and improvement of mitochondrial damage. Key words: Paclitaxel; Neuropathic pain; Resveratrol; Mitochondrial; Silent information regulator 2-related enzymes 1; Peroxisome proliferator-activated receptor-gamma coactivator 1α