A novel intelectin molecule designated sheep intelectin 2 (sITLN2) was detected in sheep abomasal mucosa. The full sequence shared 76–83% homology with other mammalian intelectins. Intelectins are mucus-associated proteins that have been shown to be up-regulated in gastrointestinal nematode infections in rodents and in human asthma. Expression of sheep abomasal ITLN2 mRNA was significantly up-regulated on day 10 post-challenge of worm-free sheep with Teladorsagia circumcincta and at day 2 in previously infected, immune sheep. Increased expression of ITLN protein following challenge was confirmed by Western blot and was immunolocalised to the mucous neck cells of the abomasal mucosa. Infection with T. circumcincta was also associated with increased levels of abomasal transcripts encoding sheep mast cell protease-1, ovine galectin-14 and IL4, which collectively suggested a Th2 type response. Intelectin may play an important role in the mucosal response to gastrointestinal nematode infections in ruminants.