Ecosystems are submitted to various abiotic stresses, among which heavy metals represent major industrial pollutants. Cadmium (Cd), that has damaging effects on plant metabolism, occurs in agricultural environments through industrial pollution and human activities, including phosphate fertiliser and sewage sludge applications. Metal availability to plants can be modulated by soil microorganisms, such as arbuscular mycorrhizal (AM) fungi. In the present work, Cd effects on the model legume Medicago truncatula inoculated or not with the AM fungus Glomus intraradices have been studied at 3 levels: (1) plant biomass production together with green part chlorophyll quantification and root isoflavonoid accumulation, (2) G. intraradices development inside roots and (3) root and shoot profiles of total proteins. A Cd concentration of 2 ppm caused a reduction of root growth, which was alleviated in colonized plants. Cd application led to an increased accumulation of some isoflavonoids [ononin, malonylononin and medicarpin-3-O-(6’-malonylglucoside)] in nonmycorrhizal roots compared to mycorrhizal roots. Metabolic markers of mycorrhization (apocarotenoids) were partly reduced in Cd treated plants. Global changes in root and shoot protein accumulation of Cd-stressed M. truncatula during the symbiotic interaction with G. intraradices were monitored by differential protein display (2-dimensional electrophoresis). Cd provoked changes in protein accumulation in root and shoot tissues, some of them being reverted by the AM symbiosis. The proteins whose abundance was modified in Cd and/or G. intraradices-treated roots and shoots were identified by LC-MS/MS and MALDI-TOF mass spectrometry, respectively. In roots, most of the proteins whose amount was increased by the mycorrhizal association belonged to metabolism category (38%), signal transduction (9%) and miscellaneous ones (9%). Interestingly, 44% of the proteins that were identified in response to Cd stress, and whose volume was reduced by the AM symbiosis, belonged to defence and cell rescue processes. RNA expression profiling was performed for the gene encoding a thaumatine-like, showing a good correspondence between transcript and protein expression profiling. In shoots, both Cd and mycorrhizal colonisation affected mainly proteins involved in the photosynthetic pathway, including several isoforms of the rubisco diphosphate carboxylase. A phosphoglycerate mutase enzyme mainly characterized the response to Cd stress of mycorrhizal plants. Results will be discussed in relation to a possible role of AM symbiosis in detoxification and/or resistance mechanisms towards Cd in M. truncatula plants.