Objectives: To evaluate the effects of a behavioral intervention, Tai Chi Chih (TCC) on circulating markers of inflammation in older adults. Design: A prospective, randomized, controlled trial with allocation to two arms, TCC and health education (HE), 16 weeks of intervention administration, and 9 weeks follow-up. Participants: A total of 83 healthy older adults, aged 59 to 86 years. Measurements: The primary endpoint was circulating levels of interleukin 6 (IL-6). Secondary outcomes were circulating levels of C-reactive protein, soluble IL-1 receptor antagonist, soluble IL-6 receptor, soluble intercellular adhesion molecule, and IL-18. Severity of depressive symptoms, sleep quality, and physical activity was also assessed over the treatment trial. Results: Among those older adults with high levels of IL-6 at entry, a trend for a treatment group by time interaction was found (F-[1,F-70] = 3.48, p = 0.07), in which TCC produced a drop of IL-6 levels comparable to those found in TCC and HE subgroups who had low levels of IL-6 at entry (t(72)'s = 0.80, 1.63, p's > 0.10), whereas IL-6 in HE remained higher than the TCC and HE subgroups with low entry IL-6 (t(72) = 2.47, p = 0.02; t(72) = 1.71, p = 0.09). Decreases in depressive symptoms in the two treatment groups correlated with decreases of IL-6 (r = 0.28, p < 0.05). None of the other cellular markers of inflammation changed in TCC versus HE. Conclusion: TCC can be considered a useful behavioral intervention to reduce circulating levels of IL-6 in older adults who show elevated levels of this inflammatory marker and are at risk for inflammation-related morbidity. (Am J Geriatr Psychiatry 2012; 20:764-772)