Objective: Early diagnosis of interstitial lung disease (ILD) is desirable not only to better define pathobiological mechanisms, but also to customize treatment protocols. As osteopontin (OPN) expression may be linked to the fibrotic remodelling in ILD, this present study was planned to evaluate the usefulness of its estimation in serum for the diagnosis of ILD.Material and Methods: Serum OPN levels were estimated by enzyme-linked immunosorbent assay in 52 diagnosed cases of ILD, that were then compared with 46 patients with chronic obstructive lung disease and 46 apparently healthy controls.Results: Median levels of serum OPN were found to be significantly higher in patients with ILD, 2.186 nanograms per milliliter (ng/ml), as compared to patients with chronic obstructive lung disease and healthy controls (1.687 and 1.923 ng/ml, respectively). The best cutoff levels of OPN, for diagnosis of ILD, was found to be >1.08 ng/ml; with a sensitivity of 88.4% and specificity of 32.6%. Of the various subtypes, serum OPN levels were found to be highest in patients with idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features; although the difference in levels between various subgroups was not found to be statistically significant (p-value=0.495).Conclusion: Serum concentration of OPN was found to be increased in patients with ILD and may be used to aid diagnosis. This opens new avenues for future research in patients with ILD, not only for the validation of the diagnostic abilities of OPN, but also as a potential target in its treatment.