Marsilea quadrifolia is a heterophile fern species belonging to wetlands populating Europe, Asia and North America. It’s internationally protected under the Habitats Directive and the Berne Convention. At the national level it has the status of endangered species in the Red List, requiring special protection and conservation measures. In Comana Natural Park it has been identified as a relatively small population in the meadow area of Neajlov. Recent researches have proved pharmacological properties against the effects of Alzheimer disease. In vitro techniques are an effective way to preserve endangered plant species both by in vitro cultures and cryopreservation. A prerequisite for the success of this approach is genetic characterization of the population to be studied. In this context, to determine the genetic polymorphism in the population a relevant number of samples was collected from different locations, given the fact that this species presents the growth and vegetative propagation of rhizomes, but also spread through sporocarps by spores. Genetic material was isolated from a total of 21 individuals from natural populations and 9 DNA samples that were qualitatively and quantitatively suitable for RAPD analysis were selected. Using the technique of amplification with decameric nonspecific primers, from a total of 41 tested there were selected 9 primers that presented a polymorphic pattern. The RAPD profiles show that polymorphism degree of the population varies with the primer tested. A high polymorphism was identified in the case of amplification with three of the primers used, while the remaining 6 have generated a smaller number of RAPD markers for intrapopulational variability. The genetic polymorphism observed in natural populations of this species is essential for adapting to changing assumptions of environmental conditions. The variability observed in natural populations of this species indicates that it can be able to adapt to changing environmental conditions.This argument isvery important concerning that the species needs aquatic habitats that are the most endangered by the temperatures rising trends at global leve l and water pollution. In the case of individuals in vitro propagated identity RAPD profiles with all the primers usedare observed, although there are some small differences in intensity of bands amplified for data quality. We can observe that there is genetic variability between the individuals regenerated. The genetic variability of the plants from the natural habitat is significat enough to ensure a future adaptation and resistance to climatic changes for this aquatic fern. The comparative spectrum of in vitro samples proves that the whole micromultiplication protocol has no genetic mutation factors and may be used as reproductible. This project was supported by Romanian Academy trough the program RO1567- IBB06/2012 and by the National Agency for Research trough PNII –RU-TD 54/2007