Objective: Although hypertension can be a complication of diabetes mellitus, hypotension and reduced pressor response to vasoconstrictor agents have been observed, especially in type 1 diabetes. The mechanisms by which this reduction occurs remain unclear, but increased expression of iNOS seems to be involved at least in male rats. We previously observed reduced contractile response induced by noradrenaline (NE) in aortas of diabetic female (DF) rats, but the mechanisms were not investigated. It has been observed that estrogen receptor (ER)β activation induces expression of iNOS in vascular smooth muscle of diabetic male rats, but nothing is known in female. The objective of this study was to investigate whether the reduction of vasoconstrictor response in aortas of DF rats is due to increased expression of iNOS/ERβ and the effects of insulin. Methods and Results: Diabetes was induced in female Wistar rats (180-200g) by an injection of alloxan (40 mg/kg) and after 3 and 15 days, treatment with iNOS inhibitor L-NIL (3 mg/kg/day/30 days) and insulin (NPH, 6IU/day/15 days) began, respectively. At the end of the treatment period, we analyzed the iNOS mRNA expression, the ER-α and ER-β protein expression by immunohistochemistry, and concentration-response curves were performed in endothelium-denuded aortic rings to NE and potassium chloride (KCl). The results are expressed as means ± S.E.M., compared by ANOVA followed by Bartlett’s test for homogeneity of variances and Tukey-Kramer multiple comparisons test. We observed that the expression of iNOS mRNA is increased in diabetic endothelium-denuded aortas (80%) in comparison to control aortas. Treatment with insulin did not correct it. The maximum contraction to NE (Control (n=6): 3.21±0.23 g; DF (n=7): 2.19±0.16 g; p < 0.05) and KCl (Control (n=8): 2.70±0.13 g; DF (n=9): 2.15±0.08 g; p < 0.05) was reduced in diabetic endothelium-denuded aortic rings. After treatment with L-NIL and insulin only the reduced maximum contraction to NE (L-NIL (n=6): 3.03±0.23 g; insulin (n=6): 3.12±0.16 g) was corrected. We found that ER-α immunostaining was similar among the groups. On the other hand, the ER-β immunostaining was increased in aorta of DF rats. Treatment with insulin, but not with L-NIL, corrected the increased ER-β immunostaining. Conclusion: Our data suggest that the increased iNOS and/or ER-β expression are involved in the reduced NE-induced contraction in DF rats, by interfering with the adrenergic receptor pathway, and not by reducing the ability of the smooth muscle to contract. The effects of the insulin treatment are selective on the adrenergic receptor pathway and may be dependent on ER-β , but not on iNOS, reduction.