Lipoxin A4 (LXA4) is an endogenous lipid mediator that is well known for its function as an inflammation resolving molecule. In addition to that, LXA4 also has anti-cancer properties related to inflammation-mediated tumorigenesis in colorectal cancer (CRC). However, the impact of LXA4 on epithelial ion transport and cell migration and proliferation in the colonic epithelium is still unknow. Yet, it was reported that LXA4 regulates airway epithelial ion transport and cell migration1,2. Thus, this study aims to investigate the putative influence of LXA4 on intestinal epithelial ion transport, cell migration and proliferation. Two colonic epithelial cell lines (T84 and HT29Cl.19A), that were originally derived from colon carcinoma tissue, were used in this study. In order to examine the impact of LXA4 on transepithelial ion transport, colonic cells were grown on filters and transepithelial ion current was recorded in Ussing chambers. For the investigation of colonic cell migration a Boyden chamber assay was used. Cell proliferation was assesses with an MTT assay and cell growth with a scratch assay. Expression of the LXA4 receptor ALX/FPR2 was investigated using western blotting, FACS (fluorescence activated cell sorting) and immunofluorescence analysis. The ALX/FPR2 receptor was expressed in T84 and HT29Cl.19A cells. Apical LXA4 (1 nM, 10 nM or 100 nM) did not influence the baseline transepithelial ion transport. However, apical LXA4 (100 nM) significantly reduced the current increase evoked by forskolin (10 uM, apical), suggesting that LXA4 inhibited cAMP-dependent ion currents in colonic cells. Furthermore, LXA4 (1 nM, 10 nM or 100 nM) reduced migration as well as proliferation of the colonic cells. In conclusion, our experiments have shown that LXA4 inhibited the cAMP-dependent ion transport as well as cell migration and proliferation of colonic cells. The LXA4-dependent reduction of cAMP-dependent ion transport might be beneficial to reduce excessive fluid loss observed in chronic inflammatory states such as colitis and the LXA4-dependent inhibition of cell migration might be important for inhibition of colonic tumorgenesis.