Nitric oxide (NO) contributes to the regulation of the fetal rat great vessels caliber. Inhibition of both NO synthases (constitutive, cNOS, and inducible, iNOS) or iNOS selectively resulted in significant reduction of the central vessels and ductus arteriosus caliber in utero. Similar regulation by NO of the cranial mesenteric artery (CMA) tone was the aim of this study. Dams were treated with a non-selective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), a selective iNOS inhibitor L-NG-(1-Iminoethyl)lysine (L-NIL), the NOS inducer, lipopolysaccharide(LPS), and the NO donor sodium nitroprusside (SNP) compared to a group of undisturbed animals (Control) N=7 all groups. On day 21 of gestation fetuses were obtained by cesarean section under anesthesia and rapidly frozen. Cryostat sections were used to measure diameters of the CMA on microscope generated images using a computer software with a built in electronic caliper. The measurements were averaged to obtain a mean diameter. The fetal CMA diameter (control 382±18.8 μm) was significantly narrowed by L-NAME(232±5.9 μm) and even more so by L-NIL (189±9.3 μm), while both LPS (472±13.7 μm) and SNP (581±26.0 μm) dilated the CMA (ANOVA < 0.0001). All group means were different from the others by multiple pairwise comparison p <0.05. Conclusions: Nitrergic control of the CMA diameter is evident. Nitric oxide from iNOS, appears to play a significant role in fetal vascular tone in contrast to the adult where iNOS has only been implicated in pathophysiological states like septic shock.