Social experience influences behavior and the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, such that WHHL rabbits exposed to a consistent, stable social experience exhibited more affiliative social behavior and less aortic atherosclerosis compared to other social groups. Oxytocin (OT) has been implicated in the expression of social behavior, stress responses, and may provide a mechanism by which social experience influences atherogenesis in WHHL rabbits. The current study examined acute and chronic changes in central and peripheral OT before and after WHHL rabbits were exposed to one of three social conditions. Cannula implanted adjacent to the hypothalamic paraventricular nucleus (PVN) allowed chronic sampling of extracellular OT concentration via microdialysis. Rabbits were exposed to one of three social conditions: an Unstable group, with initially unfamiliar rabbits paired daily for 4h during the initial week and similarly paired with a different, unfamiliar rabbit each week; a Stable group; with the same 2 littermates paired daily for 4h the entire study; and an Individually Caged group. Dialysates from the PVN and blood from the marginal ear vein were collected twice, 20 days apart, from rabbits before and after 2h of exposure to their respective social condition. Dialysates were assayed for OT and plasma was assayed for OT, catecholamines and glucocorticoids. There were no changes in PVN OT in any group following the initial social experience. In contrast, after 20 consecutive days of exposure to their respective social condition, PVN OT increased significantly in the Unstable group, but was relatively unchanged in the Stable group following the social experience on day 22. Peripheral OT was not altered in any group following the 2h social experience on day 1 or 22. The concentration of peripheral OT was the highest in the Stable group at all times. The Stable group also exhibited significantly less aortic atherosclerosis, consistent with earlier findings from our laboratory. Data from the present study suggest that the type of social experience WHHL rabbits are exposed influences PVN OT, social behavior and the progression of atherosclerosis in the WHHL rabbit model of disease.