The aim of this study was to investigate thecellular and molecular expression of tartrate resistant acid phosphatase (TRAP) as a marker of activated macrophages in macrophage dependent dextran sulphate sodium (DSS)-induced colitis in rats. In normal colon, TRAP+/CX3CR1+ macrophages were located in the upper part of the lamina propria. In the early stage (day 13) of acute colitis prior tohistopathological changes, induction of the cytokinesTNF, IL-12 and IFNgamma occurred concomitant withincreased mRNA and enzyme activity of TRAP along witha slight increase of TRAP immunolabelling in macrophages of the upper lamina propria, suggesting induction of TRAP in resident macrophages. Among these cytokines,TNFalpha up-regulated TRAP expression in the RAW 264.7 monocyte/macrophage cell line. In a later phase (day 7) with fulminant colitis, a massive infiltration of macrophages including recruited TRAP+/CCR2+ cells was observed also in the lower part of the lamina propria as well as in the submuscular layer. Additionally, diVerentiated cellularexpression of pro- and mature TRAP also suggest thatmucosal macrophages in the lower part of lamina propriabordering the sub-mucosa provide a source of replenishment of macrophages situated in the upper lamina propria.In conclusion, induction of TRAP provides an early sign of macrophage responsiveness in DSS induced colitis