Recent progress in molecular biology has provided application of gene transfer methods in arthritis. Two clinical trails using ex vivo retrovirus mediated delivery of interleukin -1 receptor antagonist gene for rheumatoid arthritis has begun in USA and Germany. However, there are still many issues to be elucidated; one is the development of gene delivery system, and the other is the selection of therapeutic gene. Arthritis is nonlethal disease, and safety is one of the important issues. Currently viral mediated vectors are major even in clinical trials however, non viral efficient gene transfer system should be developed in future. Recently the application of DNA technologies, such as antisense oligonucleotide (ODN) strategies to regulate the transcription of disease-related genes in vivo, has significant therapeutic potential. Transfection of cis-clement double-stranded oligonucleotides (decoy ODN) for nuclear factor kappaB binding site has been reported as a new powerful tool in arthritis. The concept of regulation the disease related gene expression at the level of transcriptional factor may be more therapeutic effects compared with monotherapy in arthritis.