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Populus euphratica Oliv. is a deciduous poplar species, occurring mainly in riparian areas of China and Middle Eastern countries, and presenting high tolerance to extreme temperatures and high soil salinity. In this study, an optimized protocol for development and propagation of P. euphratica from leaf explants is reported, based on a morphogenic process that involves organogenic nodule differentiation. Adventitious shoot regeneration of P. euphratica from organogenic nodules of leaf explants was achieved within a range of concentrations of alpha-naphtalenacetic acid and 6-benzylaminopurine, at a fixed 2:1 ratio. Cambial cells started to divide 5 days after inoculation on culture medium and, after 12 days, several organizing centres were already formed. Non-friable callus tissue, together with organization centres, formed structures that evolved to nodules after about 40 days which were, then, able to regenerate new shoots after 50-60 days. The nodules did not separate from the mother explants and were able to successfully give rise to new adventitious shoots. These were rescued and successfully grown and rooted in different culture media, and fully developed plants were obtained. The regeneration system here described for P. euphratica is innovative, reproducible and data from histological studies of the morphogenic process support the classification of the regenerative structures as organogenic nodules.