Direct quantitation of blood flow with radioactive microspheres in conscious spontaneously obese rats indicated that the development of obesity was associated with an elevated cardiac output and stroke volume, a normotensive blood pressure, and a reduced total peripheral resistance when directly comparing obese rats with their lean counterparts. Obesity was also associated with increased blood flow and decreased regional vascular resistance in a variety of vascular beds, whereas cardiac index and total peripheral resistance per unit of body weight were similar between groups. When corrected for tissue weight, unique alterations in flow and resistance were observed in the adipose tissue. When expressed as resistance per organ, the greatest relative alterations in vascular resistance with the development of obesity also occurred in the adipose tissue. Furthermore, localized adipose tissue expansion through cellular hypertrophy was consistently associated with a different pattern of blood flow and vascular resistance than adipose tissue that expanded through both cellular hypertrophy and hyperplasia, implying an association between depot cellularity and its hemodynamic profile.