Background Inflammation is related to many stages of atherosclerosis, and inflammatory markers have been associated with both atherosclerosis and future cardiovascular events. Descending thoracic aortic calcification (DTAC) is a manifestation of atherosclerosis, however, no previous study has examined the relationship of inflammatory markers and DTAC as detected by computed tomography (CT) in a large study. We examined whether C-reactive protein (CRP) and interleukin-6 (IL-6) are independently associated with DTAC. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that includes 6814 women and men ages 45–84 years old, all free of baseline cardiovascular disease. The inflammation markers CRP and IL-6, and DTAC by CT, quantified by Agatston score, were measured at baseline in all participants. Results We studied 6613 participants with complete data (3112 men, 3501 women, mean age 62 ± 10 years). The prevalence of DTAC was 27%. Participants with DTAC had significantly higher levels of both CRP and IL-6. After adjustment for baseline risk factors, CRP was not correlated with presence or severity of DTAC (Adjusted RR per S.D., 1.01; 95% confidence intervals 0.97; 1.05) while IL-6 associations remained significant (adjusted RR per S.D., 1.07; 95% confidence intervals 1.02; 1.14). Conclusions IL-6, a systemic inflammatory marker, is related to the presence and extent of DTAC. Further studies are needed to evaluate the interaction between DTAC and inflammation markers as predictors of future cardiovascular events.