Objective Polyinosinic-polycytidylic acid (poly IC) plays an important role in the central nervous system damage and repair.This study was to investigate the effect of poly IC on inflammatory response after spinal cord ischemia-reperfusion injury (SCIRI) in rats.Methods A total of 72 healthy adult male SD rats were equally randomized into a sham-operation, an ischemia-reperfusion (IR), and a poly IC group.The abdominal cavities of the rats were cut open and closed again in the sham-operation group and SCIRI models were established in the IR and poly IC groups by clamping the abdominal aorta, followed by reperfusion 60 minutes later and intraperitoneal injection of saline (0.1 mL) and poly IC (1.25 μg/g), respectively.At 6, 24, and 48 hours after modeling, BBB scores were obtained and the contents of TNFα, IL-1β and IFN-β were measured by ELISA.At 48 hours, the expressions of NF-κB and IL-10 were determined by immunohistochemistry, the area of ischemic necrosis in the spinal cord tissue was calculated by TTC staining, and its morphological changes were observed under the optical microscope.Results At 48 hours after modeling, the BBB scores were significantly lower in the IR and poly IC groups than in the sham-operation group (3.80±0.75 and 9.40±0.49 vs 20.00±0.00, P<0.01), though higher in the poly IC than in the IR group (P<0.01).The rats of the IR group showed extensive degenerated neurons in the gray substance of the spinal cord, with scattered foci of bleeding and blood coagulation, while those of the poly IC group exhibited fewer necrotic neurons and basically normal nuclear morphology, though with a few swelling cells.The ischemic necrosis area of the spinal cord tissue was significantly reduced.The expression of NF-κB was decreased while that of IL-10 increased markedly.Compared with the IR group, the poly IC group showed a significant increase in the expression of IFNβ (117.23±6.06 vs 55.65±4.02, P<0.01) and a remarkably decrease in the expressions of TNFα (190.45±4.16 vs 201.82±2.18, P<0.01) and IL-1β (39.27±2.48 vs 50.59±1.47, P<0.01) at 48 hours.Conclusion Poly IC can protect the spinal cord and reduce inflammatory response after spinal cord ischemia-reperfusion injury.