Although the severity of valvular calcification is an important prognostic indicator, the cellular mechanisms of the calcification process are unknown. Osteopontin modulates inflammation and biomineralization, and increased osteopontin expression has been demonstrated in calcified degenerative or rheumatic cardiac valves. The present study evaluated soluble plasma osteopontin in 32 patients with echocardiographically determined rheumatic mitral stenosis and compared the results to those of a control group of 22 healthy patients. Patients were evaluated with routine echocardiographic techniques, Wilkins scoring, and 2-dimensional echocardiographic calcium scoring. Patients with rheumatic involvement other than in the mitral valve were excluded. Plasma osteopontin and high-sensitivity C-reactive protein levels in patients with mitral stenosis were significantly higher those of the control group (p = 0.006 and p = 0.0001, respectively). A significant correlation was found between plasma osteopontin levels and the severity of mitral valve calcification (p = 0.003) and also between high-sensitivity C-reactive protein levels and Wilkins score (p = 0.009). There was a stepwise and statistically significant increase in soluble plasma osteopontin levels in association with the severity of mitral valve calcification. In conclusion, increased osteopontin levels were correlated with the severity of mitral valve calcification in patients with rheumatic mitral stenosis, suggesting an important role of osteopontin in the modulation of valvular calcification. Elevated levels of high-sensitivity C-reactive protein concentrations suggest the presence of ongoing inflammation in those patients.