Ubiquitin-proteasomal proteolytic pathway is one of the key signaling pathways determining protein degradation in muscle fibers. Among the E3 ubiquitin ligases, rate limiting enzymes of the ubiquitin-proteasomal pathway, the most interesting ones are the MuRF isoforms: MuRF-1 and MuRF-2. There are some pieces of evidence that these enzymes are also involved in the regulation of gene expression in skeletal muscle under some specific conditions (i. e. muscle disuse). We supposed that it was disuse that brought about to altered localization of MuRFs in postural muscle fibers and their translocation to nuclei. In the study using the conventional simulation model of the gravitational unloading (rat hindlimb suspension according to Ilyin and Novikov modified by Morey-Holton) we found that from the 3rd day till 14th day of unloading the content of MuRF-1 and MuRF-2 in the nuclear fraction 4-5 fold increased in unloaded soleus as compared to the control values. These data obtained by means of electrophoresis and western blot of the nuclear fraction of rat soleus were confirmed in the immunohistochemical study of co-localization of MuRF-1 and MuRF-2 antibodies and DAPI nuclear stain on transverse frozen sections of soleus muscle. Thus in the present study we observed the phenomenon of MuRF isoforms accumulation in nuclei of soleus muscle fibers during simulated gravitational unloading.