Parascaris sp. is the largest nematode parasite of horses and is responsible of equine ascaridiosis causing digestive and respiratory disorders to the animal. The fight against gastro-intestinal nematodes relies on anthelmintic treatments including macrocyclic lactones which are massively used worlwide to control human and veterinary parasites. However, control of infestation is increasingly difficult due to the emergence of resistant parasites throughout the world. The main targets of macrocyclic lactones in insects and nematodes have been identified as glutamate-gated chloride channel receptors (GluCls). However, in Parascaris sp, the mechanisms of action of macrocyclic lactones and the mechanisms of resistance remain largely unknown. First, using a candidate gene approach, we identified the orthologs of 5 genes encoding 6 GluCls subunits in Parascaris sp. The cDNAs of these subunits were amplified by PCR and cloned into a transcription vector. The corresponding cRNAs were synthesized in vitro and then microinjected into Xenopus laevis oocytes. This heterologous expression system is a powerfull tool to studied the composition and the pharmacology of recombinant receptors by recording currents after application of drugs (macrocyclic lactones) by two-electrode voltage-clamp. Thus, expression of the subunit singly or in combination in the xenopus oocytes allowed us to obtain the first functional caracterization of homeric and new heteromeric GluCl subtypes of Parascaris sp. All receptors identified are sensitive to glutamate but showed different affinity for macrocyclic lactones applied (ivermectin, moxidectin, selamectin, doramectin, emamectin, eprinomectin and abamectin). The physiological function and the impact of macrocyclic lactones on these receptors in vivo are in progress. In this study, we show the first functional characterization of Parascaris sp. GluCls sensitive to macrocyclic lactones. This research provides a better understanding of the pharmacology of GluCls as well as the mode of action of macrocyclic lactones.