Transgenic mouse models have been extensively used in Alzheimer’s disease (AD) research, although they are limited in their ability to replicate the complex process of sporadic AD, which concerns well over 95% of all AD cases. In this study, we aimed to characterize a non-transgenic rat model of tauopathy that can contribute to a better understanding of possible pathological changes, trans-synaptic spread and tau protein aggregation in AD, and find new therapeutic targets to prevent the onset or stop the spread of those pathological changes. To analyze trans-synaptic spread in Wistar rats, unilateral inoculation of tau oligomers or synthetic tau fibrils into the medial entorhinal cortex was performed, since it has been shown that the earliest neurofibrillary changes in AD brains originate in the brainstem and entorhinal cortex from where they further propagate along anatomically connected regions. Inoculation of tau oligomers and tau fibrils caused the progression of neurofibrillary changes from the entorhinal cortex to other connected brain regions, similar to AD-related changes outlined in the human brain. The development and spreading of supposedly the earliest tau pathological change, as revealed by using the AT8 monoclonal antibody to the relatively complex epitope and likely structurally important part of tau protein phosphorylated at Ser199, Ser202, and Thr205 residues, occurred much faster in animals inoculated with tau fibrils than in animals inoculated with tau oligomers. Due to a slower propagation, in animals inoculated with tau oligomers it took eleven months for all areas of the brain to be affected. In addition to neurofibrillary changes, stereotaxic inoculation of tau fibrils and tau oligomers caused the appearance of conformationally altered tau protein, formation of Gallyas- and Bielschowsy-positive inclusions that confirmed the accumulation of phosphorylated tau proteins, accumulation of amyloid , loss of synapses in the hippocampus, and significant corresponding cognitive deficits documented by using the open field test, novel object location test, novel object recognition test and T-maze test.