Pulmonary fibrosis is a chronic and progressive interstitial lung disease of known and unknown etiology. Over the past decades, macrophages have been recognized to play a significant role in IPF pathogenesis. According to their anatomical loci, macrophages can be divided to alveolar macrophages (AMs) subtypes and interstitial macrophages subtypes (IMs) with different responsibility in the damage defense response. Depending on diverse chemokines and cytokines in local microenvironments, macrophages can be induced and polarized to either classically activated (M1) or alternatively activated (M2) phenotypes in different stages of immunity. Therefore, we hypothesize that there is a “phagocytosis-secretion-immunization” network regulation of pulmonary macrophages related to a number of chemokines and cytokines. In this paper, we summarize and discuss the role of chemokines and cytokines involved in the “phagocytosis-secretion-immunization” network regulation mechanism of pulmonary macrophages, pointing toward novel therapeutic approaches based on the network target regulation in the field. Therapeutic strategies focused on modifying the chemokines, cytokines and the network are promising for the pharmacotherapy of IPF. Some Traditional Chinese medicines may have more superiorities in delaying the progression of pulmonary fibrosis for their multi-target activities of this network regulation.