Recently, the efficacy of macrolide antibiotics in cystic fibrosis and bleomycin-induced lung injury was reported. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by structural abnormalities including stromal fibrosis. Fibroblasts are resident cells thought to play an important role in the development of fibrosis. Although the effect of Roxithromycin (RXM) on inflammatory cells is well known, there is no evidence on the effect of RXM on fibroblasts. The purpose of the present study was two-fold: to examine the effect of RXM on the growth of fibroblasts in vitro and to examine the effect of RXM on the proliferation of fibroblasts in vivo. Nasal polyp fibroblast lines were generated from untreated patients, and those who were treated with RXM (300 mg/day) for one month before biopsy. Nasal polyp fibroblast lines from untreated patients were cultured for 72 hours with or without RXM, and the direct effect of RXM on fibroblast growth in vitro was examined by cell counting and 3H thymidine uptake. Next, we examined the in vivo effect of RXM on nasal polyp fibroblasts (NPFs) by comparing the growth characteristics of NPF lines from RXM treated and untreated patients. Finally, we examined the proliferating rate of NPF lines from the same patient before and after treatment with RXM. NPF lines that were treated with RXM exhibited a lower proliferating rate in vitro as compared to those that were not treated with RXM. Treatment of NPF lines with RXM suppressed the proliferation of fibroblasts in a dose-dependent manner. In addition, NPF lines from patients treated with RXM exhibited a lower proliferating rate in vitro as compared to NPF lines from the same patient taken before RXM treatment. We demonstrated that RXM directly suppressed nasal polyp fibroblast proliferation, and that this effect of RXM on fibroblast growth was persistent, indicating that RXM may prevent the progression of nasal polyposis by inhibiting the development of fibrosis.