Abstract: Objective To assess the electroporation(EP)as non-viral gene vectors for gene therapy of osteoarthritis(OA). Methods Healthy male SD rats aged 8 weeks were selected.OA model was induced by medial meniscus forefoot resection and anterior cruciate ligament transection in the right knee.EP with interleukin-1 receptor antagonist(IL-1Ra)was locally performed in the joints of rats at 1 week after induction of OA.According to the treatments, rats were randomly divided into four groups: non-treated arthritis as OA group(n=15); IL-1Ra plasmid treated arthritis without transfection performed as NP(naked plasmid)group(n=15); IL-1Ra plasmid treated arthritis and following electroporation as EP group(n=15); non-arthritic rats as normal group(n=15).Rats in different groups were sacrificed at 1-, 2-, 3-, 4-week after treatment, and isolated knee joints at 1 week post-treatment, IL-1Ra and IL-1β mRNA levels in the tissue of cartilage and synovium were analyzed using real-time PCR, and the protein content in the synovial fluid were analyzed by ELISA.In addition, gross appearance examination and histological evaluations were performed and the pathology sections were stained with hematoxylin, eosin(H-E)and Toluidine blue at 4 weeks post-treatment. Results In OA and NP groups, cartilage in medial femoral condyle were largely damaged, in EP group, the cartilage surface was intact and smooth.Pathology results showed that cartilage in OA and NP groups were severely damaged, extracellular matrix loss considerably, while in EP group, the damage was limited in cartilage surface at 4 weeks.The IL-1Ra expression of EP was significantly higher than other groups(P＜0.01), and it was 4.29 times more than the normal group.Compared with normal group, IL-1β gene expression in EP group showed no significant difference during observation period(P＞ 0.05).And the results of ELISA and PCR were accorded. Conclusion IL-1Ra transfected by electroporation can inhibit the development of osteoarthritis, which provides new tools for clinical study of gene therapy of osteoarthritis.