Tumor microenvironment (TME) is hypoxic and low pH. TME confer not only resistance of anti-cancer drug therapy on tumor cells, but also impair the activity of immune cells. Under TME condition, tumor-infiltrated macrophages (Mfs) change phenotype from anti-tumor (M1) phenotype to tumor progressive (M2) phenotype. Previously we reported that prolyl hydroxylase (PHD) inhibitor, which activate hypoxia-induced factors (HIFs), improve TME. In this study, we examined whether the improvement of TME by PHD-inhibitor activate tumor-infiltrated Mfs. Lewis lung carcinoma cells were subcutaneously transplanted into right frank of mice which aged at 8-12 weeks. Mice were treated with PHD inhibitors intraperitoneally at day 10 after tumor transplantation. Then tumor tissues were collected at day 16 and analyzed immune cells by immunofluorescence staining and flowcytometry. We performed phagocytosis assay using sorted Mfs from tumor tissue and bone derived Mfs. Furthermore, we injected sorted Mfs into the tumor and evaluated tumor growth. PHD-inhibitor inhibited tumor growth. We concluded that PHD inhibitor directly activated Mfs and TME improvement supported activity of Mfs.