The anxiety level in the rats is correlated to the interleukin-2 (IL-2) in the brain. The present study aimed at investigating the effects of dioscorea (will yam), a Chinese medicine, on the emotional behavior and the IL-2 level in the brain of ovariectomized (OVX) rats. One month after the ovariectomy, female Wistar rats were screened by using the elevated plus-maze (EPM) test for measuring the anxiety level and were then orally administered by dioscorea (250, 750, and 1500 mg/kg/day). Three weeks later, these animals were then tested again in the EPM and in the forced swim (FS) test. The anxiety level was highly increased in a half of the OVX rats, but not in the other half one. Chronic administration of dioscorea, at doses of 750 and 1500 mg/kg/day, exerted anxiolytic activity in HA OVX rats. However, lower dose of dioscorea, 250 mg/kg/day, increased the anxiety level in LA OVX rats. These behavioral data were compatible with the findings in IL-2, where the IL-2 level in the cerebral cortex of HA OVX rats was significantly attenuated by the treatment of dioscorea, but the IL-2 level in the prefrontal cortex of LA OVX rats was enhanced by the dioscorea at 250 mg/kg/day. Learned helplessness in the FS test was inhibited by the dioscorea at 1500 mg/kg/day. The present results provide new insight into the role of IL-2 in the individual differences of anxiety in the postmenopausal animals. The psychoneuroimmunological function needs to be taken into account when measure the behavioral effects of dioscorea.