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Background Detomidine is an α‐2 agonist sedative drug which reduces the release of norepinephrine in nerves. Administering this drug through intranasal (IN) route could cause direct transmission to the central nervous system. Therefore, IN administration of detomidine would decrease the side effects and the onset of sedation. Objectives In this study, IN administration of detomidine in sheep through an atomiser was compared to its IV administration. Methods Fifteen mature female sheep with an approximate weight of 49.53 ± 1.72 kg were used. They were randomly divided into three groups: (1) atomising 10 μg/kg (IND 10 ); (2) IV 10 μg/kg (IVD) and (3) atomising 30 μg/kg (IND 30 ). Following administration, vital signs, electrocardiographic components, sedative score and biochemistry profile were measured after 15, 30 and 60 min, which were compared with the baseline measures. Results Bradycardia and the percentage of reduction from the baseline value in the respiratory rate were lower in the IND 10 group compared to those in the IVD group. There was no significant difference in terms of the temperature and blood oxygen saturation (SpO 2 ) among all the groups ( p > 0.05). The level of cortisol declined in all the groups, and in the IND 30 (60 min), it was significantly different with the baseline value. The level of glucose increased in all the groups compared to the baseline, which was not significant. Insulin concentration was reduced in all the groups, and in the IND 30 group, it changed significantly 60 min after the drug administration. Sedation onset time was faster in the IV group. However, sedation scores between the two administration methods were not different, and only a dose‐dependent increase was found in the sedation score in the atomisation group. Conclusions Our findings revealed that IN atomisation of detomidine triggers similar sedation as its IV administration, which could be used as an alternative method.