Background and Aims: In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrin alpha 4 beta 1 on leukocytes has previously been reported in animal models. Although the integrin alpha 4 beta 1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrin alpha 4 beta 1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs). Methods: We measured the expression levels of integrin alpha 4 beta 1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 +/- 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 +/- 4.6 years old). Results: Recombinant IL-17A up-regulated expression levels of integrin alpha 4 beta 1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrin alpha 4 beta 1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrin alpha 4 beta 1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects. Conclusions: These findings suggest that up-regulated levels of integrin alpha 4 beta 1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.