Objectives: To investigate the molecular mechanisms behind warm needling using Cdna microarray technology, thus providing further scientific evidence for its efficacy. Method: Ten patients with knee OA of kidney-yang deficiency were selected for 2 weeks of warm needling treatment. This treatment involved stimulating the selected acupoints using needles with a burning moxa stick on their handle for 40 minutes per session. Accumulated clinical scores of kidney-yang deficiency were assessed pretreatment and posttreatment using a 40-factor questionnaire of OA with kidney-yang deficiency. Four patients with the best therapeutic efficacy were selected for cDNA microarray testing. The significantly expressed genes were screened through Significance Analysis of Microarray (SAM) for further functionally annotated. Results: 32 significantly expressed genes were screened. GO and PATHWAY annotation results of these genes showed that immune and signal transduction functional genes and pathways significantly expressed. Conclusion: This work demonstrates that the molecular mechanism behind warm needling treatment may be associated with the regulation of immune and signal transduction genes and pathways.