Circulating microRNAs are protected from degradation by their association with either vesicles or components of the RNAi machinery. Although increasing evidence indicates that cell-free microRNAs are transported in body fluids by different types of vesicles, current research mainly focuses on the characterization of exosome-associated microRNAs. However, as isolation and characterization of exosomes is challenging, it is yet unclear whether exosomes or other vesicular elements circulating in serum are the most reliable source for discovering disease-associated biomarkers. In this study, circulating microRNAs associated to the vesicular and non-vesicular fraction of sera isolated from partially hepatectomized rats were measured. Here we show that independently from their origin, levels of miR-122, miR-192, miR-194 and Let-7a are up-regulated two days after partial hepatectomy. The inflammation-associated miR-150 and miR-155 are up-regulated in the vesicular-fraction only, while the regeneration-associated miR-21 and miR-33 are up-regulated in the vesicular- and down-regulated in the non-vesicular fraction. Our study shows for the first time the modulation of non-vesicular microRNAs in animals recovering from partial hepatectomy, suggesting that, in the search for novel disease-associated biomarkers, the profiling of either vesicular or non-vesicular microRNAs may be more relevant than the analysis of microRNAs isolated from unfractionated serum.