Background: Usual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival. Several growth factors such as IGFs (insulin-like growth factors) and IGFBPs (insulin-like growth factor binding proteins) seem to take part to this pathogenesis. Pirfenidone is an immunosuppressant drug that is thought to have anti-inflammatory and anti-fibrotic effects both in vitro and in vivo. Objective: To assess IGFBP1 and IGFBP2 as non-invasive biomarkers for prediction and outcomes of UIP clinical activity and therapeutic response to the anti-fibrotic pirfenidone. Results: Serum levels of IGFBP1 and IGFBP2 were significantly higher in the UIP group than in the healthy subjects (p ≤ 0.005). After 6 months therapy, UIP patients were divided into 2 groups according to improvement in MRC dyspnea grading into clinically improved and non-improved groups. 6MWT and SPaO2 were significantly improved in the clinically improved group compared to the non-improved one with no differences as regards other parameters (p < 0.0001). Both IGFBP1 and IGFBP2 were significantly decreased in serum while only IGFBP2 was decreased in BAL of all UIP after completing 12 months therapy. Conclusion: IGFBP1 and IGFBP2 were increased in active UIP patients and reduced after 12 months anti-fibrosing therapy. IGFBPs may be promising biomarkers and predictors of response to therapy in UIP. Keywords: IGFBP1, IGFBP2, UIP, Anti-fibrotic pirfenidone