Tissue transglutaminase (TG2) expressed in monocytes and macrophage is known to participate in processes during either early and resolution stages of inflammation. The alternative splicing of tissue transglutaminase gene is a mechanism that increases its functional diversity. Four spliced variants are known with truncated C-terminal domains (TGM2_v2, TGM2_v3, TGM2_v4a, TGM2_v4b) but scarce information is available about its expression in human monocyte and macrophages.We studied the expression of canonical TG2 (TGM2_v1) and its short spliced variants by RT-PCR during differentiation of TPH-1 derived macrophages (dTHP-1) using two protocols (condition I and II) that differ in Phorbol-12-myristate-13-acetate dose and time schedule. The production of TNF-α and IL-1β in supernatant of dTHP-1, measured by ELISA in supernatants showed higher proinflammatory milieu in condition I.We found that the expression of all mRNA TG2 spliced variants were up-regulated during macrophage differentiation and after IFN-γ treatment of dTHP-1 cells in both conditions. Nevertheless, the relative fold increase or TGM2_v3 in relation with TGM2_v1 was higher only with the condition I.M1/M2-like THP-1 macrophages obtained with IFN-γ/IL-4 treatments showed that the up-regulation of TGM2_v1 induced by IL-4 was higher in relation with any short spliced variants. The qualitative profile of relative contribution of spliced variants in M1/M2-like THP-1 cells showed a trend to higher expression of TGM2_v3 in the inflammatory functional phenotype.Our results contribute to the knowledge about TG2 spliced variants in the biology of monocyte/macrophage cells and show how the differentiation conditions can alter their expression and cell function.