A large amount of evidence suggests that acupuncture stimulation enhances the experimental pain threshold in various animal models. Acupuncture analgesia is mediated by the endogenous opioid system, and the analgesic response to acupuncture shows individual variation. This study identified and characterized the genes that differ between high responders (HR) and low responders (LR) on acupuncture stimulation, using a cDNA microarray. Fifteen participants were stimulated at the LI 4 acupuncture point, and the finger withdrawal latency (FWL) test was performed to classify the HR and LR groups. Total RNA was then extracted from blood samples from each group and used as a template to synthesize cDNA. The cDNA was applied to Code Link UniSet Human 20K microarray chips. The Symptom Checklist 90-Revised (SCL-90-R) was also analyzed as a measure of psychological variation. The FWL was significantly elevated in the HR group after acupuncture stimulation, whereas there was little increase in the LR group. The ratio of HR to LR subjects was 9:6. We found that 353 and 22 genes were up- and downregulated, respectively, in the HR group. However, the SCL-90-R profiles did not differ significantly between the two groups. These results suggest that the individual variation in acupuncture analgesia, verified by measuring the FWL in the HR and LR groups, resulted from genetic inheritance rather than differences in the psychological environment.