Mechanisms underlying development of lung fibrosis in severe asthma have been unclear. In our murine models of mild and severe asthma, lung fibrosis was significantly developed only in the severe asthma model. RNA-seq analyses revealed that not only genes of collagen type 1 but also genes of matrix metalloproteinases (MMPs) and activins, TGF-b family cytokines were found to be highly expressed in the lung of the severe asthma model compared with that of the mild model. More interestingly, pathway analyses showed that pathway of CCR5 and the ligands were up-regulated in the severe model. In this study, roles of CCR5 in the development of lung fibrosis in the severe model were analyzed. Treatment with a CCR5 antagonist, maraviroc but not dexamethasone exerted significant inhibition of the development of lung fibrosis. Interstitial macrophages (IMs) that expressed CCR5 were markedly increased in the lung, and the degree was significantly higher in the lung of severe asthma model than that of the mild asthma model. Real-time RT-PCR analyses revealed that IMs derived from the lung of severe model expressed higher mRNA levels of MMPs and activins than those of mild asthma model. From these results, it was strongly suggested that CCR5⁺ IMs were possibly involved in the development of the lung fibrosis in severe asthma.