AIM: To determine whether there are changes in NO production in the carotid arteries of TFF3-/- mice and their controls (WT) that are on a high-salt diet compared to mice of the same strain consuming a low-salt diet measured by direct fluorescence. STUDY DESIGN: Experimental study on an animal model. MATERIALS AND METHODS: Healthy TFF3-/- mice and their WT controls, aged 10-11 weeks divided into 4 groups (N=10 per group), were used in this study. Part of the mice (both strains, i.e. two groups) consumed food with increased NaCl (4%), and part (second two groups) food with low salt content (0,4%) for 7 days. On the eight day, the animals were anesthetized, sacrificed by decapitation and their carotid arteries were isolated. NO production was measured in vitro, by direct fluorescence on carotid artery samples under basal conditions and after blood vessel stimulation by changes in fluid flow in the chamber for isolated perfused vessels. Measurement of NO production took place in basal conditions and in the presence of eNOS inhibitor L-NAME. RESULTS: The results show that basal NO production (no flow) was significantly reduced in WT mice on a high-salt diet. L-NAME significantly reduced NO production in all groups except Tff3-/- HS mice. Under flow conditions, NO production was lower in WT HS mice. NO production in TFF3-/- HS mice was similar to that in TFF3-/- LS, as in both WT groups. L-NAME did not affect NO production in TFF3-/- HS mice, but significantly reduced NO production in the other three groups. CONCLUSION: Research has shown that a high-salt diet affects the level of oxidative stress and changes in NO production in WT mice, while TFF3-/- mice were less susceptible to the effects of a high-salt diet.