The mesolimbic dopamine system, that plays a pivotal role in emotionally motivated behaviours, originates in the ventral tegmental area (VTA) and sends major projections to the nucleus accumbens (Acb). In the present work, we assessed the effects of manipulation in the mesolimbic dopaminergic system identified with the “brain reward system” on the percentage of peripheral blood lymphocytes in freely moving rats differing in locomotor activity to novelty (high responders; HR or low responders; LR). T and B lymphocyte populations were determined by flow cytometry (CD3-FITC/CD45RA-PC7). Peripheral blood was collected from rats exposed to chronic 14 day VTA electrical stimulation to obtain feeding or exploration response (constant current 0.1 ms duration, cathodal pulses, 50 Hz, 30-min daily session) and with a lesion electrode aimed at Acb: 3 weeks after electrode implantation, after 2 weeks of chronic VTA stimulation, on the 2nd day after the Acb lesion (2mA for 15s) and on the 14th VTA stimulation day following the Acb lesion. As compared to the respective sham animals, chronic stimulation of the VTA caused significant (p<0.05) decrease in T cell percentage in both HR (33.32 ± 5.39% vs 48.04 ± 7.45%) and LR (44.99 ± 2.94% vs 51 ± 3.57%) animals. In addition, significantly (p<0.05) lower level of T cell percentage in HR animals (40.13±3.64% vs 50.94 ± 5.87%) rats were observed. On the 14th VTA stimulation day following the Acb lesion, significant (p<0.05) decrease in B cell percentage in both HR (12.47 ± 3.55% vs 19.45 ± 1.58%) and LR (7.09 ± 2.48% vs 16.5 ± 3.46%) animals was observed. On the other hand, chronic stimulation of the VTA (20.99 ± 3.38% vs 17.65 ± 0.49%) and Acb lesion (25.14 ± 2.48% vs 20.62 ± 0.85%) caused significant increase (p<0.05) in B cell percentage in HR animals. The results emphasize the importance of individual differences (HR vs LR) in the influence of the mesolimbic motivational system on blood lymphocyte distribution.