Objective: To investigate the correlation between the change in expression of the tumor associated macrophage (TAM) markers CD68 and CD206 and the clinicopathological parameters. Methods: We retrospectively analyzed 28 PGI-DLBCL patients by immunohistochemical stainning. The surface expression of biomarkers CD68 and CD206 on TAMs in samples obtained at diagnosis was compared with that in specimens obtained at first relapse. Based on the change in expression levels of CD68 and CD206 from diagnosis to relapse, patients were categorized into three groups: “increased”, “stable” and “decreased”. Results: A significant difference was observed between the three groups with respect to CD68 and CD206 expressions (P=0.012) and there existed a consistency between the two (P=0.008). The three groups showed a negative correlation with age, sex, stage, B symptoms, diagnosis, ECOG performance status, and IPI scores, while a positive correlation was observed with the site of lesion of CD206 expression (P=0.032). The time to relapse (TTR) in the three groups of CD68 and CD206 was not significantly different (P=0.23, P=0.818). Conclusion: Our study suggests that increase in CD206 and decrease in CD68 expression at relapse indicates M1-TAM polarization into M2-TAM, which plays an important role in PGI-DLBCL relapse. Furthermore, M2-TAM polarization may be associated with the site of Primary gastric diffuse large B lymphoma.