Background: Ulcerative colitis (UC), one of the main disorders among inflammatory bowel diseases, is associated with reduced colonic smooth muscle contractility and causes motility disturbances. It is characterised by abdominal pain, diarrhea, gastrointestinal bleeding, rectal bleeding and loss of body weight. Recent studies showed that transient receptor potential vanilloid 4 (TRPV4) stimulation may be associated with the inflammatory response in UC and its blockade may be preventive for this disease. So far, data is not available about the effect of deletion of this channel on colonic motility in UC cases. Aim: The aim of the present study was to examine the consequences of TRPV4 deletion on the development of UC and colon motility in a murine model of dextran sulfate sodium (DSS)-induced colitis. Methods: The administration of 2.5% DSS, in drinking water ad libitum, in male C57BL/6 wild type (WT) and TRPV4 knockout (TRPV4KO) mice for three different durations of treatment induced UC. Mice were divided into eight groups of WT and TRPV4KO (V4) mice. The groups included the controls (WT-C, V4-C), DSS-treated for 3 days (WT-D3, V4-D3), DSS-treated for 7 days (WT-D7, V4-D7) and DSS- treated for 10 days (WT-D10, V4-D10). Colitis activity was assessed by percentage change of body weight and by measuring colon length. It was further assessed by noticing stool consistency, rectal and colonic bleeding. Segments of mouse distal colon were suspended in organ bath chambers containing 10 mL of oxygenated Ringer's solution to record spontaneous colonic motility and the changes in tension generated by addition of acetylcholine (ACh) and carbachol. In addition, an ELISA kit was used to measure myeloperoxidase (MPO) concentrations in colon tissue. Tissues were stained with Hematoxylin-Eosin and Masson-Trichrome stains for histopathological assessment. Results: All mice treated with DSS for 3 days exhibited a decrease in body weight gain and with longer periods of DSS treatment, a significant decrease in body weight was observed. The colon length of all DSS-treated mice was significantly shorter compared to the controls and all the mice except those treated for three days, had soft stool, rectal and colonic bleeding. DSS administration decreased frequency and amplitude of colonic motility. The sensitivity to ACh increased in both WT-D3 and V4-D3 while in WT-D7 and V4-D7 it was decreased to the level of control. Data obtained by carbachol was inconsistent and not conclusive. MPO concentrations were significantly lower in WT-D10 and this effect was not seen in V4-D10. Histopathological assessment revealed that the colonic tissue of TRPV4KO mice was affected to a lesser extent, in terms of the inflammation, tissue damage and fibrosis, compared to WT mice. Conclusion: Our data suggests that the lack of TRPV4 attenuates the severity of inflammation that develops immediately after DSS administration (in first three days), which results in less severe complications of such as mucosal loss, dysmotility and fibrosis.