Colonic mucus can be divided in a loosely and a firmly adherent layer. The mucus consists of one gel forming mucin, Muc2, and membrane-anchored mucins, such as Muc1. Here we investigated the colonic mucus thickness and accumulation rate in vivo in anaesthetized mice and the importance of the two different mucin genes by using Muc1-/- or Muc2-/- mice. We also investigated the importance of mucus as protection against colitis induced by dextran sodium sulphate (DSS, 3% in the drinking water). Mucus thickness was measured with micropipettes, The severity of the inflammation was valuated and presented as Disease activity index (DAI). The firmly adherent mucus layer was significantly thinner in the Muc1-/- mice than in the wt. The Muc2-/- mice had hardly any firmly adherent mucus. After induction of colitis the firmly adherent mucus layer decreased in the wt and the DAI in this group reached 2.1 ± 0.2. The firmly adherent mucus layer increased after DSS treatment in the Muc1-/- mice and the DAI was lower than in the wt group. The Muc2-/- mice developed a very severe inflammation in the colon within 24 hours with a DAI close to max and an almost total lack of mucus. In conclusion: both layers of adherent mucus consist of Muc2 mucins. The reduction of the mucus thickness in the mice lacking the gene for Muc1 might depend on Muc1 being important for Muc2 mucins to be produced or anchored to the mucosa. Muc2 mucins are important in protecting the mucosa against DSS induced colitis.