We studied the influence of diabetes on norepinephrine (NE)-induced changes in intracellular free Ca2+ levels (receptor-mediated Ca2+ signaling) in single tail artery vascular smooth muscle (VSM) cells. VSM cells from 12-16 week streptozotocin-induced diabetic (SID) rats showed an increase in sensitivity to NE when compared to control VSM cells in that the concentration of NE needed to elicit half maximal response of the initial Ca2+ transient was reduced more than 4-fold though the maximal response attained was apparently reduced. In addition, the slope factor (steepness) of the dose-response relation was lowered 4-fold. Moreover, VSM cells of diabetic animals had a higher incidence of NE-induced Ca2+ oscillatory responses. The shift of the dose-response curve to the left, coupled with a higher incidence of oscillations, indicate that the noradrenergic receptor-mediated Ca2+ signaling pathways in tail artery VSM of diabetic rat may be altered.